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Empowering Personalized Cancer Treatment

A letter from our CEO

Thank you for choosing CGI Laboratories as a partner in the clinical management of your patients.

CGI Laboratories is the clinical laboratory of Cancer Genetics, Inc. (CGI), which is located in

Rutherford, New Jersey. Cancer Genetics, Inc. was founded in 1999 by world-renowned cytogeneticist

Dr. R.S.K. Chaganti, whose vision was to establish an oncology reference laboratory with R&D

capabilities to impact the personalized treatment of cancer. Since its inception, CGI has emerged as a

leader in the field of personalized oncology with products and services that are improving patient

management and reducing healthcare costs. To achieve our vision, CGI has developed a corporate

culture that inspires innovation, respects knowledge, and fosters leadership. In recognition of this culture,

we were acknowledged by The Scientist as one of the top 20 best places to work within the industry.

Our laboratory is GCP and HIPAA compliant, CLIA certified, CAP accredited, and holds licensure in

several US States. We monitor and improve our performance through a variety of methods, such as

external audits, satisfaction surveys, and proficiency testing (CAP and New York State).

CGI’s dedicated staff takes pride in being accessible to our clients, in providing superior turnaround

time, and in developing new and innovative tests. Our cutting-edge proprietary tests provide critical

genomic information to clinicians to assist with the diagnosis, prognosis and therapeutic guidance of

hematological, urogenital and HPV-associated cancers. By leveraging the expertise of our clinical and

scientific team, which has over 15 years of diagnostic experience, we are able to provide clients with

comprehensive diagnostic information.

Our staff is committed to Empowering Personalized Cancer Treatment™ and we welcome the opportunity to serve you and your patients.

Panna Sharma CEO and President


Table of Contents

Introduction to CGI Laboratories

A. Our Unique Approach to Personalized Medicine 5

B. Our Clients 6

C. Our Staff 6

Methodologies and Tests

A. What We Do 11

B. Description of Tests Offered 12

Specimen Collection

A. Sending Your Specimens 21

B. Specimen Requirements 21

C. Handling of a Bone Marrow Specimen “Dry Tap” 24

D. Labeling Instructions 24

E. Requesting Samples 25

F. Test Requisition Forms 25

Billing

A. Billing Policy 31

B. CPT Codes 32

Reporting

A. Accessing Patient Reports 35

B. Laboratory Reports 37

1

2

3

4

5

Table of Contents

Licenses and Accreditations

A. Quality Control Program 39

B. Licenses and Credentials 39

C. Confidentiality 40

D. Compliance Statement 41

CGI Expand Dx™

43

CGI Select OneSM

47

Sample Reports

6

7

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A. Our Unique Approach to Personalized Medicine

CGI’s full service laboratory is focused on providing comprehensive diagnostic, prognostic and theranostic information on hematological, solid, urogenital, and HPV-associated malignancies. Our services are all based upon expertise in cancer testing with an emphasis on personalized patient care. To ensure proper specimen management and quick turnaround time (TAT), all services are performed in our CLIA certified and CAP accredited laboratory.

We continuously expand our test menu as new technologies and biomarkers of clinical utility are developed. Below is a quick overview of our services and proprietary products.

A novel microarray for the clinical management of mature B-cell neoplasms MatBA

® is a proprietary product designed

by CGI for the detection of specific chromosomal gains and losses frequently observed in mature B-cell neoplasms. To learn more, see section 2 (page 19) or visit www.cgimatba.com.

A custom array for both the diagnosis and prognosis of kidney, bladder and prostate cancers UroGenRA

TM is CGI’s custom

oligonucleotide array product line designed to detect genomic gains and losses that frequently occur in kidney, bladder and prostate cancers. To learn more, see section 2 (page 20).

FISH-based HPV-Associated Cancer Test FHACT

TM is a proprietary FISH test designed by

CGI for HPV-associated cancers. CGI’s first application of FHACT

TM analyzes copy number changes of 4 chromosomal

regions frequently observed in precancerous and cancerous cervical cells that may be used in the triage of women prior to referral for colposcopy. To learn more, contact us at [email protected] or visit http://www.cancergeneticsitalia.com/dna-fish-probe/fhact/.

1

Milestones 1999 CGI is founded by Dr. R.S.K.

Chaganti in Cambridge, MA.

2005 CGI moves to Hackensack, NJ.

CLIA certified laboratory. ~ Dx Laboratory: Cytogenetics,

FISH, Molecular Genetics. ~ R&D: DNA-FISH Probes.

2008 CGI moves to Rutherford, NJ.

2009 CGI increases lab services

~ Dx Laboratory: Cytogenetics, FISH, Molecular Genetics, Flow Cytometry, Histology, Immunohistochemistry.

~ R&D: DNA-FISH Probes, Array CGH.

2010 MatBA

®-CLL CLIA approved for

clinical use.

SummationTM

Report is developed

2011 Launch of CLL Complete

SM program.

MatBA®-CLL New York State

licensed.

CGI establishes oncology-focused clinical trial services, Select One™.

Expansion of Dx lab services: ~ JAK2 & MPL mutation analysis ~ EGFR mutation analysis.

2012 MatBA

®-SLL CLIA & New York

State approved for clinical use.

Expansion of Dx Lab services: ~ Solid tumor, ALK Break Apart

FISH, BRAF & KRAS mutation analysis.

~ Expansion of CLL CompleteSM

testing; NOTCH1 & TP53 mutation added.

2013 MatBA

®-DLBCL CLIA & New York

State approved for clinical use.

UroGenRATM

-Kidney CLIA & New York State approved for clinical use.

Launch of DLBCL CompleteSM

program.

Expansion of CLL CompleteSM

testing; SF3B1 mutation added.

MatBA®-MCL submitted for

regulatory approvals.

http://www.cgimatba.com/

mailto:[email protected]

http://www.cancergeneticsitalia.com/dna-fish-probe/fhact/

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A. Our Unique Approach to Personalized Medicine

A comprehensive and integrated clinical report

SummationTM

is a CGI-developed comprehensive one page, full-color diagnostic summary report of all test results, which provides a definitive diagnosis/prognosis. Through the report, clinicians are empowered to provide patients with a more personalized clinical treatment. To learn more, see section 5 (page 37).

An integrative test program

CompleteSM

is a proprietary test menu developed by CGI to assist physicians in the diagnosis, prognosis, and therapy selection for CLL/SLL and DLBCL patients. Complete

SM is a comprehensive list of tests that integrates the latest prognostic

molecular markers for the clinical management of CLL/SLL and DLBCL. To learn more, see section 5 (page 37) or visit www.cancergenetics.com/laboratory-services/cll-complete.

An outreach program for community laboratories

CGI Expand Dx™ is an initiative offered to community laboratories to expand their pathology services through a joint collaboration with CGI Laboratories. CGI Expand Dx™ builds on the capabilities of the community laboratory, increases efficiency, and drives revenue growth. To learn more, see section 7 (page 43) or visit www.cgiexpanddx.com.

A unique solution to support clinical research

CGI Select OneSM

is a program offered to clinical trial clients such as, CROs and biopharma. The program’s goal is to design solutions that deliver dependable results, reduce the associated costs of clinical trials, and enable early “go/no-go” decisions. To learn more, see section 8 (page 47) or visit http://cancergenetics.com/laboratory-services/selectone/.

B. Our Clients

CGI provides services to a wide variety of providers and organization throughout the United States & globally, below is a quick overview of our client base:

Hematology/Oncology Practices

Pathology Departments

Reference Laboratories

Hospital and University Medical Centers

Biotech and Pharmaceutical Companies

C. Our Staff

The services we provide are supported not only by research, but also by the highest technical quality derived from a panel of prominent scientific and medical advisors within the oncology diagnostic field. Our senior staff and department directors are highly trained and have on average over 15 years of experience along with post-doctoral studies in the field of cytogenetics and molecular genetics. CGI’s scientific advisory board includes leading specialists within the field of cancer pathology, clinical cytogenetics, and hematopoietic neoplasms and as thought leaders they have the ability to drive adoption within the field of cancer diagnostics.

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http://www.xxxxxx.com/

http://www.xxxxxx.com/

http://www.cgiexpanddx.com/

http://cancergenetics.com/laboratory-services/selectone/

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C. Our Staff

Raju S.K. Chaganti, Ph.D., is the founder of CGI and has served as chairman of the board of directors since the company’s inception. Dr. Chaganti is an internationally recognized leader in cancer cytogenetics and molecular genetics. He is a co-discoverer of patents for the cloning of two genes rearranged in lymphoma translocations, BCL6 and BCL8, and an additional two patents for the detection of translocations for the FISH classification of kidney cancers. Currently, Dr. Chaganti is the incumbent of the William Snee E. Chair at Memorial Sloan-Kettering Cancer Center (MSKCC) and is a faculty member of the Department of Medicine and Cell Biology Program. He is also a professor at both the Gernster Sloan-Kettering

Graduate School of Biomedical Sciences and at the Biochemistry, Cell and Molecular Biology Program at Wiell-Cornel Graduate School of Medical Sciences in New York City. Dr. Chaganti was previously the chief of MSKCC’s cytogenetics service department, which he established in 1976; the department as one of the earliest genetically based cancer diagnostic services in the country.

Dr. Chaganti received a Ph.D. in biology (genetics) from Harvard University Graduate School of Arts and Sciences and completed his post-doctoral training at the Medical Research Council of Great Britain. Additionally, he completed a sabbatical in the Department of Tumor Biology at Karolinska Institute Stockholm, where he focused on experimental murine and tumorigenesis as well as immunology. Dr. Chaganti is certified by American Board of Medical Genetics in medical genetics with a subspecialty in clinical cytogenetics.

Lan Wang, M.D., joined CGI in 2007 and specializes in diagnostic hematopathology with a focus on lymphomas and leukemias. Her work has been published in numerous peer-reviewed publications. Dr. Wang is an active member of the Society of Hematopathology, the United States and Canadian Academy of Pathology, and the College of American Pathologists. Dr. Wang completed her residency training in Anatomic and Clinical Pathology, and fellowship in Hematopathology at Massachusetts General Hospital, Harvard Medical School. Dr. Wang is certified by the American Board of Pathology in Anatomical and Clinical Pathology, as well as Hematopathology. In New Jersey, Dr. Wang holds a Medical License and

Bioanalytical Laboratory Director License from the Board of Medical Examiners. She also has a certificate of qualification from the state of New York as a Laboratory Director in Histopathology, Cytopathology, Hematology, Immunohematology, Oncology-Molecular and Cellular Tumor Markers, and Cellular Immunology-Malignant Leukocyte Immunophenotyping.

Dr. Wang holds the position of Staff Pathologist/Hematophathologist and cancer liaison physician at the Chilton Hospital in New Jersey and at Hackensack UMC at Mountainside Hospital. She is also the medical director for the Division of Pathology at Mountainside Hospital. Upon joining CGI, Dr. Wang monitored the setup of CGI’s anatomical pathology and flow cytometry laboratories and through her leadership the laboratory has grown significantly in volume and testing. She also steered CGI’s focus in becoming a full-service laboratory that targets hematological oncologists and pathologists.

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C. Our Staff

Weiyi Chen, Ph.D., HCLD, joined CGI in 2005 and is scientifically focused on the identification and characterization of genomic alterations in B-cell lymphoma and the prognostic implications of such alterations using modern molecular techniques, such as microarrays. Her post-doctoral training was in the Cell Biology Program at Memorial Sloan-Kettering Cancer Center (MSKCC). Dr. Chen is certified as a High-Complexity Clinical Laboratory Director (HCLD) by the American Board of Bioanalysis (ABB) and also has a certificate of qualification as a laboratory director from the New York State Department of Health. She is also an active member of the Association of Molecular Pathology.

Since joining CGI, Dr. Chen has supervised the establishment of the molecular diagnostic laboratory and not only validated clinical assays at CGI but also acquired licensure from the Clinical Laboratory Improvement Amendment (CLIA) and the state of New York for such assays. She also oversaw the setting up of an automated system in CGI’s molecular diagnostic lab. Dr. Chen now manages the operation of the molecular lab, reviews and reports test results, and directs the development and validation of new clinical tests.

Pal Singh-Kahlon, Ph.D., FACMG, is board certified by the American Board of Medical Genetics (ABMG) in Clinical Cytogenetics and he also holds a certificate of qualification from the NYS Health Department as a lab director in Cytogenetics. In the state of NJ, the Board of Examiners has granted him a Bioanalytical Lab director's license in Cytogenetics. He brings more than 30 years of experience in clinical cytogenetics to CGI since joining in 2010. He has nearly 20 years of experience as a director in various positions, including seven years in oncology at leading commercial cytogenetics laboratories, such as LabCorp and Genzyme. He was trained at the University of California School of Medicine in San Francisco and is an active member of the American

College of Medical Genetics (ACMG), the American Society of Human Genetics (ASHG), and the Association of Molecular Pathology (AMP).

Since joining CGI, Dr. Singh-Kahlon has focused on delivering high quality diagnostic reports while improving on the industry leading turnaround times. He is also involved in the expansion of CGI’s FISH test menu and has introduced new tests such as the purified plasma cell (PPC) FISH, which is used in the diagnosis of multiple myeloma. He has furthered CGI’s FISH testing by validating molecular markers such as HER2/neu and ALK, which are used in the clinical management of solid tumors.

V. Subhadra Nandula, Ph.D., FACMG, is board certified by the American Board of Medical Genetics (ABMG) in Clinical Cytogenetics. She also holds a certificate of qualification from the New York Department of health in cytogenetics. Dr. Nandula’s focus has been on human genetics and especially cytogenetics for over 15 years. She spent 10 years at Columbia University and has published over 30 articles in international peer-reviewed journals. Experienced in solid tumor analysis, she has worked for over 7 years in HER-2/neu and oligodendroglioma FISH testing. In addition, she has a strong background in blood borne cancers that became valuable to CGI when she joined in 2012. As Associate Director of Cytogenetics at CGI, Dr. Nandula

works closely with our team to invigilates turn-around-time and monitor quality control.

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C. Our Staff

Kelly Corcoran, Ph.D., joined CGI in 2008. Her previous research has been focused on stem cell and breast cancer. Prior to joining CGI, Dr. Corcoran was awarded the New Jersey Commission on Science and Technology Fellowship where she took an industry postdoctoral at Chromocell Corporation. There, she led the Stem Cell Therapy Project for the treatment of HIV, optimized proprietary Chromovert technology for application in Cell Therapy and Stem Cell biology, and played a key role in the generation of stable, clone ion channel cell lines and multigene, stable, clonal G-Protein Coupled Receptors (GPCR) cell lines.

At CGI, Dr. Corcoran has successfully obtained certification from the College of American Pathologists (CAP) for the clinical flow cytometry lab. She has developed and optimized the leukemia/lymphoma antibody panel as well as developed several Standard Operating Procedures for sample handling, preparation, and machine quality control. She is responsible for training and managing flow technicians and has led the validation of the ZAP-70 test.

Jane Houldsworth, Ph.D., joined CGI in 2007. She has over 20 years of experience in translational research and has a long standing interest in the biology and genetics of lymphoma and male germ cell tumors. Dr. Houldsworth has published more than 50 peer-reviewed papers, 15 chapters, and continues to consult on academic research projects. She is also a reviewer for multiple scientific journals. Dr. Houldsworth is an active member of the American Society of Hematology (ASH) and the American Association for Cancer Research (AACR). She was awarded several grants from the National Institutes of Health, the Lance Armstrong Foundation, and other private foundations. In 2005, Dr. Houldsworth attained her New York State certificate of qualification

as a laboratory director for oncology, molecular and cellular tumor markers.

Before joining CGI, Dr. Houldsworth was an Associate Attending Geneticist and an Associate Laboratory Member at Dr. R.S.K. Chaganti’s laboratory at the Memorial Sloan-Kettering Cancer Center. As Vice President of the Research and Development Department, she leads several ongoing research projects including the establishment of proprietary FISH-based testing and the development of CGH microarrays, such as the Mature B-cell Array (MatBA

®).

Our Account Management Team

CGI prides itself on emphasizing a personal approach to cancer treatment and diagnostics. Thus, we employ only the most attentive and knowledgeable staff, so each client’s need is addressed in accordance with their expectations. Our highly experienced account management team has on average over 15 years of experience and knowledge in the laboratory and diagnostic sector. CGI’s account managers ensure that the unique needs of our clients are met. From the moment a client begins working with CGI, an account manager is assigned to work with the client through each step, ensuring no question is left unanswered. Our aim is to provide individualized service to each client; thus, the same account manager exclusively handles an entire account.

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A. What We Do

At CGI, we utilize a vast number of diagnostic tests to ensure the most comprehensive results for each patient we service. The tests are categorized into five diagnostic areas:

Flow Cytometry

Anatomic Pathology

Cytogenetics

Fluorescence in situ Hybridization (FISH)

Molecular Diagnostics

We provide our clients with a detailed report for each requested test along with a SummationTM

report, which integrates all the requested tests into a one-page, full-color, comprehensive report. The Summation

TM report provides a definitive diagnosis, which results in quick and efficient decision-

making.

The Flow Cytometry department is centered on immunophenotyping hematolymphoid malignancies using antibodies directed against cell surface and cytosolic markers to characterize cells of interest. The results are used in conjunction with morphologic assessment to diagnose lymphoma or leukemia.

The Anatomic Pathology department performs histologic evaluation of solid tissue and cytologic studies on non-gynecological fluids, smears, and fine needle aspiration (FNA) specimens.

The Cytogenetics department processes bone marrow (BM), leukemic peripheral blood (LPB), and lymph node/tissue biopsies, which are utilized in setting up tissue cultures to be used in chromosomal analysis. Specimens are tested for leukemias, lymphomas, myelodysplastic syndrome (MDS), myeloproliferative diseases (MPD), and other hematopoietic malignancies. This process is used for diagnosis and as a means to monitor both therapy-related and residual disease changes in the malignancy.

FISH testing is conducted complementary to cytogenetic analysis. It is a molecular cytogenetic technique used to either confirm chromosomal findings or to monitor changes after therapy. This process is used for both hematopoietic and solid tumor malignancies and is generally composed of FISH panels with multiple gene probes to test different neoplasia. The department also provides plasma cell purification for the multiple myeloma panel.

The Molecular Diagnostics department offers testing in hematological and other cancers using many advanced technologies. The laboratory is equipped with cutting-edge platforms such as 3130 Genetic Analyzer, 7500 DX Real-time PCR system (FDA Approved), Pyromark Q24 pyrosequencing, EZ1 Advanced XL DNA/RNA automated purification system, QIAxcel capillary electrophoresis system, and Agilent microarray scanner. The department’s highly experienced laboratory scientists are dedicated to providing a high degree of quality and efficiency in clinical molecular testing services.

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B. Description of Tests Offered

Flow Cytometry: Panels

Lymphoid: CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11c, CD19, CD20, CD23, CD38, CD45, CD56, CD57, Kappa, Lambda

Myeloid/Lymphoid/Acute Leukemia: CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11b, CD11c,CD13, CD14, CD15,CD16 CD19, CD20, CD22, CD23, CD33, CD34, CD38, CD45, CD56, CD57, CD64, CD71, CD117, HLA-DR, Kappa, Lambda

Paroxysmal Nocturnal Hemoglobinuria (PNH)*: CD14, CD16, CD45, CD55, CD59, CD235a (Glycophorin A), FLAER

*PNH tests are used to detect the exact proportion of PNH cells in the blood.

Plasma Cell Neoplasms: CD4, CD8, CD3, CD7, CD10, CD19, CD20, CD28, CD34, CD38, CD45, CD56, CD117, CD138, sKappa, sLambda, cKappa, cLambda, cIgM, cIgA, cIgG

ZAP-70**: CD3, CD5, CD19, ZAP-70, CD45

**ZAP-70 tests are used in assessing the prognosis and need for aggressive therapy in patients with chronic lymphocytic leukemia (CLL).

Also available: MPO, TdT, CD1a, CD79a, CD25, CD41, CD43, CD61, CD103, FMC7

Anatomic Pathology

Tests in the area of morphology include both histology and cytology. We offer tissue in situ hybridization (ISH) and a full immunohistochemistry (IHC) library including over 150 antibodies (see next page) with a core expertise in hematological tumors and common solid tumors. IHC stains can be ordered as global or technical component only. Atypical urine cytology results will be reflexed to UroVysion

® (FISH).

Peripheral Blood Smears, Chronic Lymphocytic Leukemia (CLL).

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Anatomic Pathology: Antibody Listing

IHC

SMA (Actin, Smooth Muscle)

CD30

DOG1

Lambda

PMS2

MSA (Actin, Muscle Specific)

CD31

E-cadherin

Lysozyme

P.carinii (Pneumocystis Carinii)

ALK1

CD33

EGFR (Epidermal Growth Factor Receptor)

Mammaglobin

Podoplanin (D2-40)

Annexin A1

CD34

EMA (Epithelial Membrane Antigen)

MART-1/melan A

PR (Progesterone Receptor)

Basal Cell Cocktail (34BE12 + p63)

CD43

Ep-CAM (Epithelial Specific Antigen)

Melanosome (HMB-45)

PSA (Prostate Specific Antigen)

bcl-2

CD45 (LCA)

Epithelial Related Antigen (moc31)

Mesothelin

PSAP (Prostatic Acid Phosphatase)

bcl-6

CD45RO

EBV (Epstein-Barr Virus) LMP

MLH1

RCC (Renal Cell Carcinoma)

BOB.1

CD56

ER (Estrogen Receptor)

MSH2

S100

c-KIT (CD117)

CD57

Factor VIII Related Antigen

MSH6

SOX-2

CA 19-9

CD61

Factor XIIIa

MUM1

Synaptophysin

CA 125

CD68

Fascin

MBP (Myelin Basic Protein)

TAG-72

Calcitonin

CD79a

Fli-1

Myeloperoxidase (MPO)

TdT (Terminal Deoxynucleotidyl Transferase)

Caldesmon

CD99

GCDFP-15

Myogenin

Thyroglobulin

Calponin-1

CD138 (Syndecan-1)

GFAP (Glial Fibrillary Acidic Protein)

Myoglobin

Toxoplasma (Toxo)

Calretinin

CD163

Glycophorin A

Myosin, Smooth Muscle (heavy chain)

TTF-1 (Thyroid Transcription Factor-1)

CEA (Carcinoembryonic Antigen)

CDX-2

Granzyme B

Napsin A

TRAcP (Tartrate-Resistant Acid Phosphatase)

CD1a

Chromogranin A

Helicobacter pylori

Neurofilament

Tryptase

CD2

Cytomegalovirus (CMV)

HepPar-1 (HSA)

NSE (Neuron Specific Enolase)

Tyrosinase

CD3

COX-2 (Cyclooxygenase 2)

HER-2/neu, PATHWAY

Oct2

Villin

CD4

Cyclin D1

HHV-8 (Human Herpes Virus Type 8)

Oct4

Vimentin

CD5

Cytokeratin 903

HSV I&II

p16

WT1

CD7

Cytokeratin (CAM 5.2)

hCG (Human Chorionic Gonadotropin)

p27kip1

ISH

CD8

Cytokeratin (Pan) AE1/AE3

hGH (Human Growth Hormone )

p53

EBER

CD10

Cytokeratin 17

IgA (Immunoglobulin A)

p57kip2

Kappa

CD14

Cytokeratin 19

IgD (Immunoglobulin D)

p63

Lambda

CD15

Cytokeratin 20

IgG (Immunoglobulin G)

PTH (Parathyroid Hormone )

CD20

Cytokeratin 5/6

IgM (Immunoglobulin M)

PAROVIRUS B19

CD21

Cytokeratin 7

Inhibin

PAX2

CD22

Cytokeratin 8

Insulin

PAX5

CD23

Cytokeratin 8 &18

Kappa

PAX8

CD25

Desmin

Ki-67

PLAP (Placental like Alkaline Phosphatase)

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Cytogenetics: Karyotype

Diagnosis and prognosis in cytogenetics includes karyotyping with reflex to FISH.

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Normal Karyotype

Abnormal Karyotype

46,XY

49,XY,der(1;6)(q10;p10),+der(1;6)(q10;p10),+3, t(8;22)(q24;q11.2),-13,+15,+18

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FISH: Probes and Panels

In addition to individual probes for specific subsets, our FISH menu includes the following panels:

Hematologic Tumors

Acute Lymphocytic Leukemia (ALL) B-ALL PEDIATRIC/ADULT

Acute Lymphocytic Leukemia (ALL) T-ALL

Acute Myeloid Leukemia (AML)

11q23 (MLL-Break Apart) t(9;22) (BCR/ABL/ASS) 17p13 (TP53) t(12;21) (ETV6/RUNX1) 9p21 (p16/CDKN2A) CEP4, 10, 17

14q11 (TCR-Alfa/Delta Break Apart)

t(8;21) (ETO/AML1) [M2] t(15;17) (PML/RARA) [M3] inv(16) (CBFB-Break Apart) [M4,

Eos] 11q23 (MLL-Break Apart)

Anaplastic Large Cell Lymphoma (ALCL)

Chronic Lymphocytic Leukemia (CLL)

Chronic Myelogenous Leukemia (CML)

2p23 (ALK-Break Apart) 11q22.3 (ATM)/17p13 (TP53) CEP12/13q14

(D13S319)/13q34 CEP6/6q23 (c-MYB) t(11;14) (CCND1/IGH)

t(9;22) (BCR/ABL/ASS)

CML in blast crisis t(9;22) (BCR/ABL/ASS) 17p13 (TP53) CEP8

Multiple Myeloma (MM) ‡† with

purified plasma cells (PPC) Myelodysplastic Syndrome (MDS) Myeloproliferative Disease (MPD)‡

13q14/13q34 17p13 (TP53) 1p/1q D5S23/D5S72/CEP9/CEP15 t(4;14) (FGFR3/IGH) t(11;14) (CCND1/IGH) t(14;16) (lGH/MAF) Also Available IGH-Break Apart CEP7/CEP11 t(6;14) (CCND3/IGH) t(14;20) (IGH/MAFB)

5p15.2/5q31 CEP7/7q31 CEP8 20q12 11q23 (MLL-Break Apart)

4q12 (FIP1L1/CHIC2/PDGFRA) 5q33 (PDGFRB-Break Apart) BCR/ABL (BCR/ABL/ASS) CEP8/CEP9

Non-Hodgkin’s Lymphoma (NHL)‡ BM Transplant Monitoring

Burkitt t(8;14) (MYC/IGH)

DLBCL 3q27 (BCL6-Break Apart)

Follicular t(14;18) (IGH/BCL2)

Mantle t(11;14)(CCND1/IGH)

MALT Lymphoma MALT1-Break Apart

Also Available

IGH-Break Apart c-MYC-Break Apart

CEP X/Y

Solid Tumors ALK-Break Apart (NSCLC) PathVysion® (HER2/neu) (Breast) UroVysion® (Bladder)

‡Note: The respective probe should be selected from the panel based on the patient’s diagnosis.

†Note: Combinations of these probes are used for Myeloma relapse, MGUS & light chain amyloidosis.

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FISH: CLL Panel Images

Molecular Diagnostics: Tests

Our molecular diagnostics menu includes the following tests:

Acute Myeloid Leukemia (AML) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

CEBPA mutation analysis c-KIT mutation analysis (Exon 8 and 17) FLT3 mutation analysis (ITD, D835)

NPM1 mutation analysis (Exon 12)

MatBA®- CLL/SLL Array CGH

IGHV mutation analysis NOTCH1 mutation analysis

TP53 mutation analysis SF3B1 mutation analysis

Chronic Myeloid Leukemia (CML) Lymphoma

ABL kinase domain mutation BCR-ABL (PCR) quantitative

~ Major (p210) (IS)

~ Minor (p190)

BCR-ABL (PCR) qualitative

~ Major (p210)

~ Minor (p190)

B-Cell Clonality (IGH)

T-Cell Clonality (TCR) T-Cell Clonality (TCRβ) MatBA

®-DLBCL Array CGH

MatBA®-MCL Array CGH

SETRATM

: Six Gene Expression Treatment Response Assay

Non-CML Myeloproliferative Neoplasms (MPN) Solid Tumor

c-KIT mutation (systemic mastocytosis) (D816) JAK2 V617F mutation analysis

~ Reflex to MPL515/505

~ Reflex to JAK2 Exon 12

JAK2 Exon12 mutation analysis MPL515/505 mutation analysis

KRAS mutation (CRC, NSCLC) BRAF mutation (CRC) EGFR mutation (NSCLC)

NRAS mutation (CRC, Melanoma, Thyroid

cancer) UroGenRA

TM-Kidney Array CGH (Diagnosis –

Subtype)

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17p13.1/11q22.3 CEP12/13q14/13q34 11q13/14q32 CEP6/6q21

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Molecular Diagnostics: Test Descriptions

ABL Kinase domain mutation analysis The ABL Kinase domain mutation is associated with a poor prognosis and a high risk of progression. Among the ABL Kinase domain mutations, the presence of T315I mutation confers the highest resistance to imatinib, dasatinib, and nilotinib.

BCR-ABL t(9;22) quantitative and qualitative RT qPCR assay The assay is designed to monitor BCR-ABL transcript levels following the TKI treatment. It can detect 1 CML cell in the background of 100,000 normal cells and provides greater sensitivity versus conventional cytogenetics or FISH. Results are reported per the International Scale (IS) as a percentage ratio of BCR-ABL/ABL. The BCR-ABL fusion transcript is generally found in a majority of CML cases, in a subset of ALL cases, and occasionally in AML cases. The qualitative BCR-ABL test is designed to help establish the initial diagnosis of CML and/or Philadelphia-positive ALL.

BRAF mutation analysis The presence of BRAF mutation is important information for treatment and management of colorectal cancer (CRC), melanoma and hairy cell leukemia. It is associated with a poor prognosis and a lack of response to EGFR inhibitor therapies. In metastatic melanoma, BRAF V600E mutations are associated with response to BRAF inhibitor (e.g. Zelboraf

®) therapies. V600E BRAF mutations are

the most common kinase mutation in melanoma cases (60%).

c-KIT mutation analysis The test is used for prognostic stratification of AML patients. The presence of a c-KIT mutation in Exon 8 and 17 increases the risk of relapse in patients with karyotypes such as t(8;21)(q22;q22) and/or inv(16). The c-KIT mutation (D816) has also been observed in most cases of Systemic Mastocytosis (SM) and detection of the c-KIT mutation can assist with the initial diagnosis of SM and treatment response.

CEBPA mutation analysis The CEBPA mutation is used for risk stratification of AML patients. CEBPA mutations have been observed in ~10% of cytogenomic normal (CN-AML) cases and are associated with a favorable prognosis. Recent literature suggests that only patients with double (Biallelic) CEBPA mutations have a favorable prognosis. The test is often ordered as a reflexed test with FLT3 and NPM1.

EGFR mutation analysis The presence of EGFR mutation is important to the treatment and management of non-small cell lung cancer (NSCLC). Patients with mutations such as deletion in Exon 19, point mutations in Exon 21 (L858R, L861Q), or Exon 18 (G719x) have been associated with an increased responsiveness to EGFR TKI therapy (gefitinib or erlotinib). However, cases with mutations in Exon 20 (T790M and S768I) are associated with resistance to EGFR TKI therapy and disease progression.

FLT3 mutation analysis The analysis is used for prognostic stratification of AML patients. Mutations (internal tandem duplication) of the FLT3 gene are strongly associated with a poor prognosis.

IGHV mutation analysis Analysis of IGHV mutation is used to assess the prognosis of patients with CLL. Patients presenting the IGHV mutation tend to have a more favorable prognosis, with a longer overall survival.

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Molecular Diagnostics: Test Descriptions

JAK2 Exon12 mutation analysis In JAK2 V617F-negative patients, mutations in exon 12 are found in patients with polycythemia vera with the presence of erythrocytosis. The test is often ordered as a reflexed test with JAK2 V617F.

JAK2 V617F mutation analysis The JAK2 V617F mutation is found is less than 90% of patients with polycythemiaveva (PV) and in nearly 50% of patients with thrombocythemia (ET) or primary myelofibrosis (PMF). The mutation is a major criteria for establishing the diagnosis of myeloproliferative neoplasms (MPN).

KRAS mutation analysis The presence of KRAS mutation is important to the treatment and management of colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) as it is associated with a poor prognosis and a lack of response to EGFR inhibitor therapies.

MPL515/505 mutation analysis Somatic mutations of codons 515 and 505 in the myeloproliferative leukemia (MPL) virus oncogene are clonal markers of ET and PMF. The markers are used to diagnosis the diseases and is often ordered as a reflexed test with JAK2 V617F.

NOTCH1 mutation analysis NOTCH1 mutations has been observed in ~10% of CLL cases at diagnosis and is more frequently associated with advanced CLL and IGHV un-mutated cases. NOTCH1 mutations predict a shorter overall survival, a shorter time to first treatment (TTFT), and a higher risk of Richter transformation.

NPM1 mutation analysis The analysis is used in the prognostic stratification of AML patients. Mutations of the NPM1 gene have been observed in ~50% of cytogenetically normal AML patients and are associated with a favorable prognosis in the absence of FLT3 mutations. However, NPM1 mutations do not impact the poor outcome of patients with FLT3/ITD.

SF3B1 mutation analysis SF3B1 mutations are independent predictors that occur in 10-15% of CLL patients. They are indicative of shorter time to treatment, and a poorer overall survival.

SETRATM (Six Gene Expression Treatment Response Assay) This result from this assay allows for the risk stratification of DLBCL patients according to the expression level of six genes determined by RT qPCR. The assay measures the expression level of three genes associated with prolonged survival (LMO2, FN1, BCL6) and three genes associated with short survival (CCND2, SCYA3, BCL2).

TCR, TCR, and IGH gene rearrangement assay

Detection of TCR, TCR, or IGH gene clonal rearrangement identifies the presence of T-cell or B-cell clonal expansion and provides a confirmative diagnosis of lymphoma.

TP53 mutation analysis TP53 mutation is an independent marker used in the prognosis of CLL patients and is found in ~10% of such patients. A majority of CLL patients with deletion of 17p13 also exhibit TP53 mutations; however, ~5% of CLL patients with TP53 mutation do not exhibit 17p13 deletion. In CLL cases, the presence of TP53 mutation, with or without deletion of 17p13, is associated with shorter progression-free survival, overall survival, and refractory to chemotherapy.

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MatBA® Array CGH

Mature B-cell Array, or MatBA®, is the generic name for CGI’s Array CGH product line. The array is

designed to detect specific chromosomal gains and losses that are frequently observed in mature B-cell neoplasms. Mature B-cell neoplasms arises in B-cells that have entered germinal centers within lymph nodes as part of the immune’s response. The neoplasms displays great heterogeneity at the clinical, pathologic, and genetic levels and diagnosis is dependent on the pathologic examination of biopsy material.

MatBA® is intended to support the diagnosis and prognosis of

Non-Hodgkin’s Lymphoma (NHL) in the following cases:

Chronic Lymphocytic Leukemia/Small Cell Leukemia (CLL/SLL)

Diffuse Large B-cell Lymphoma (DLBCL)

Mantle Cell Lymphoma (MCL)

Follicular Lymphoma (FL) The MatBA

® Array CGH is designed for use in a clinical laboratory and is optimized for use on a

range of specimen types, such as peripheral blood (PB), bone marrow (BM), cell suspension, and formalin-fixed paraffin-embedded (FFPE) tissue specimens. The MatBA

®-CLL/SLL Array CGH and

MatBA®-DLBCL Array CGH have been approved by both CLIA and the state of New York as an

assay for routine prognostication in CLL/SLL and DLBCL cases. To learn more, please visit www.cgimatba.com.

MatBA®-CLL/SLL Array CGH detects the loss of 13q (2 sites: MIR-15A/16.1

and RB1), 17p (TP53), 11q (ATM), and 8p, and the gain of chromosome 12, 2p, 8q, and 3q, which are indicative of prognosis of CLL. The test assays genomic alterations by array comparative genomic hybridization (array CGH), which enables the simultaneous detection of gain/loss at multiple loci

not currently assessed by other conventional methodologies.

MatBA®-DLBCL Array CGH detects both individual markers gain of 3q22-

q27, 8q24 (MYC), 18q21 (BCL2) and the loss of 6q21 (PRDM1), 6q23.3-q24 (TNFAIP3), and 8p23.3-p21.3) and genomic imbalances of the CDKN2A-TP53-RB-E2F (reflective of a complex pattern of copy number alterations) that are associated with adverse outcome. The test assays genomic

alterations by array comparative genomic hybridization (array CGH), which enables the simultaneous detection of gain/loss at multiple loci not currently assessed by other conventional methodologies.

MatBA®-MCL Array CGH detects the loss of 8p, 9p (CDKN2A), 9q, 13q, and

17p (TP53), and the gain of 3q and 12q which associate with shorter overall patient survival with current therapies. It also detects the loss of 8p and gain of 8q (MYC) which have been found to be associated with leukemic presentation/progression and the loss of 6q that correlates with poor

outcome in leukemic MCL. The test assays genomic alterations by array comparative genomic hybridization (array CGH), which enables the simultaneous detection of gain/loss at multiple loci not currently assessed by other conventional methodologies.

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UroGenRATM Array CGH

UroGenRATM

, CGI’s custom oligonucleotide array product line, is designed to detect genomic copy number alterations (CNA) with prognostic and diagnostic value in kidney, prostate and bladder cancers. It was designed to detect gains and losses that frequently occur in genetic material in these three cancer types and has the potential to differentially diagnose and/or stratify patients to assist in and guide clinical management. The first application of UroGenRA

TM Array CGH, UroGenRA

TM-Kidney is both

CLIA and New York State approved.

UroGenRATM

-Kidney Array CGH is specifically designed to classify kidney cancers or renal cell carcinoma (RCC) into three major malignant subtypes: clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chrRCC), and one benign: oncocytoma (OC), which is critical to patient management and

treatment protocols. The assay detects 16 specific chromosomal gains and losses that are used in CGI’s proprietary aCGH-based decision tree to properly subtype the patient’s RCC. Subtyping kidney cancers is critical for decisions on treatment selection especially for those cases that consider surgical intervention or drug trials for those with metastatic disease or “unclassified” renal cancers. Genomic alterations are assayed in the current test by array CGH to classify both needle biopsies and surgically-resected renal specimens

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Specimen Collection

B. Sending Your Specimens

When you first sign up with CGI, your account representative will help you determine your specific courier needs, which are decided according to your geographical location. Our service runs both day and night, based upon our clients’ schedules, to ensure that our clients are able to continue to operate according to their own established schedule. FedEx is available for all clients outside of our local geographic region. Regardless of the method used, CGI will provide prompt and efficient service to ensure that clients receive results in a timely manner. Our accessioning office can be reached by phone (888)334-4988, or by email [email protected].

C. Specimen Requirements

Receiving Your Specimens

Optimal specimen requirements will vary depending on the disease being investigated. Proper collection and handling of specimens ensure reliable test results and decrease compromised specimens. All specimens received are inspected and logged into our tracking system according to defined protocols. This serves in maintaining the quality of the specimen, issuing timely reports, and preventing patient information discrepancies.

Note: The requirements for a UroVysion® analysis is 25-50 ml of urine in a suitable container for

same day shipping; PreservCyt® should be used if the specimen will remain in transit for more than a

day to ensure stability. See page 22-23 for other specimen requirements.

Compromised Specimens

All specimens are treated as potentially hazardous or infectious as described by established OSHA guidelines on Standard Precautions. Compromised specimens may yield unreliable results, or may require additional steps during analysis to optimize results. Thus, CGI will identify any specimens that are considered compromised; notify technical staff and clients of consequent special attention in processing or evaluation. CGI will make every effort to analyze all specimens received, but some may be sufficiently compromised to warrant rejection.

Our clients are contacted in all cases of compromised samples and explained the possibility of substandard results. It is at the discretion of the Section Supervisor whether or not to proceed with compromised specimens. If specimen is rejected, an explanation of the reasons will be included in a Notification of Rejected Specimen Form and faxed to the client.

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Specimen Collection

B. Specimen Requirements

TEST PERIPHERAL BLOOD BONE MARROW TISSUE

Blood Smear Aspirate Smear Core Clot

BLOOD EVALUATION

2 Green/ NaHeparin tubes (3-5 mL) Room Temp AND 1 Lavender/ EDTA tube (3-5 ml) Room Temp.

1-2 air-dried smears (optional)

BONE MARROW EVALUATION

1 Lavender/ EDTA tube (3-5 ml) Room Temp.

2 Green/ NaHeparin tubes (3-5 ml) Room Temp. AND 1 Lavender/ EDTA tube (3-5 ml) Room Temp.

4-8 bedside smears

>1 cm (length) in formalin jar

>1 cm (length) in formalin jar

FLOW CYTOMETRY

1 Green/ NaHeparin tube (3-5 ml) Room Temp. OR 1 Lavender/ EDTA tube (3-5 ml) Room Temp.

1 Green/ NaHeparin tube (3-5 ml) Room Temp. OR 1 Lavender/ EDTA (3-5 ml) Room Temp.

Fresh Tissue/ FNA/Lymph nodes in RPMI media Refrigerated

HISTOPATHOLOGY Formalin Fixed

CYTOGENETICS/ FISH

1 Green/ NaHeparin tube (3-5 ml) Room Temp.

1 Green/ NaHeparin tube (3-5 ml) Room Temp.

Formalin fixed paraffin embedded tissue block or fresh tissue in RPMI

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Specimen Collection

B. Specimen Requirements

TEST PERIPHERAL BLOOD BONE MARROW TISSUE

Blood Smear Aspirate Smear Core Clot

MOLECULAR PATHOLOGY

DNA Test


1 Lavender/ EDTA) tube (2-3 ml) Room Temp.

Formalin fixed paraffin embedded tissue block OR

6 x 8 m sections OR 4-6 sections in 8

m thickness on slides with an additional H & E stained slide. Room Temp.

RNA Test

1 Lavender/ EDTA tube (3-5 ml) Room Temp. OR Cold Pad within 48hrs after collection

1 Lavender/ EDTA) tube (2-3 ml) Room Temp. OR Cold Pad within 48hrs after collection

ARRAY CGH



5 x 10 m sections OR 3 x 1.5 mm core punches

ARRAY CGH

3-4 core needle biopsies (18-gauge needle preferred) (frozen) OR Minimum of 0.2 cm

3 tissue with an

H & E stained slide transported frozen

CLL COMPLETESM



DLBCL COMPLETESM



Formalin fixed paraffin embedded tissue block or fresh tissue

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Specimen Collection

C. Handling of a Bone Marrow Specimen “Dry Tap”

CGI has a very high success rate with limited amounts of marrow as well as with more cellular aspirate specimens.

The following specimen collection method can help our hemato-pathologists to reach a conclusive diagnosis on these types of specimens:

1. Collect 2 or more bone marrow core biopsies

a. Make 5-10 touch imprint slides from the biopsies (for Cytology and Morphology)

Be sure to keep slides AWAY FROM FORMALIN Do not place open formalin jar anywhere near slides as the formalin fumes may affect

the quality of morphologic evaluation Let all slides AIR DRY COMPLETELY before placing in the plastic container to

prevent smudging

b. Place the 1st bone marrow core biopsy in a Formalin jar (for Histology and IHC testing)

c. Place the 2nd biopsy in RPMI media (for Flow Cytometry and/or Cytogenetics testing)

Store in refrigerator until shipped

d. Additional samples/clot should be submitted for histology

2. Indicate on REQUISITION that the specimen is a “DRY TAP”

3. Collect a peripheral blood specimen in a Sodium Heparin or green top tube (for possible Flow Cytometry and/or FISH testing, if indicated)

4. Collect a peripheral blood specimen in an EDTA or purple top tube (for possible molecular testing, if indicated)

5. Place each specimen in the Biohazard bag before placing in kit

6. Call 888-334-4988 or 201-528-9187 for a specimen pickup or contact your local account representative or client services if you have any questions.

D. Labeling Instructions

Based on regulatory requirements, all specimen containers must be labeled with at least two patient identifiers such as, patient name and date of birth. Also, the collection dates and times must be on either the requisition or specimen container.

All specimens received in the laboratory must have a completed requisition form with all appropriate information filled out, including:

Patient name

Patient DOB

Collection data/time

Specimen type/site

Requesting physician

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Specimen Collection

E. Requesting Samples

Supplies and containers for our laboratory services are permitted by State and Federal laws. CGI will provide you, at no charge, with all the supplies you need: requisition forms, tubes, packaging transport forms, etc. Supply requests can be submitted to us by contacting your account manager or by contacting our accessioning department. You can reach the department by phone at (888) 334-4988 or by email [email protected].

F. Test Requisition Forms

Each specimen must be submitted to CGI with a fully completed test requisition form. Types of test requisition forms:

Hematology/Oncology

Pathology

Solid Tumor

Urology

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Bone Marrow Specimen Transport Kit Peripheral Blood Specimen Transport Kit


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Specimen Collection


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Hematology/Oncology Test Requisition Form

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Specimen Collection


3

Pathology Test Requisition Form

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Specimen Collection


3

Solid Tumor Test Requisition Form

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Specimen Collection


Urology Test Requisition Form

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Billing

A. Billing Policy

Our primary focus is to ensure excellence in the personalization of cancer treatment by simplifying and providing visibility into our billing processes. Occasionally, CGI may request necessary adjustments within the guidelines of the law. However, it is in direct conflict with CMS and BIPA guidelines to avoid attempts at collecting reimbursement or to routinely waive co-pays and deductibles. Our policy is to ensure that non-government and non-contracted payors pay at reasonable commercial rates. As part of this effort, we certify that our billing is compliant with the U.S. Code and National Standards and agree to the following:

1. Accept the amount reimbursed by your patients' insurance.

2. Bill clients according to the Explanation of Benefits (EOB) provided by the patient's insurance

carrier.

3. If CGI is instructed by the health plan to bill for co-pays and deductibles, then we are required

by law to adhere to such instructions.

4. To never issue a balance bill to you or your patients.

5. Your patients will only be responsible for meeting their co-pays and deductibles as assigned.

We are required to demonstrate to the Centers for Medicare and Medicaid Service (CMS) that we make an effort to collect at or above the Medicare rates. When billing a third party insurance, our practices are:

1. To make a minimum of three attempts to collect from the payor.

2. To notify the patient, if CGI is unable to collect from the payor.

3. To make every effort to become a participating provider for a carrier that has been identified

as a non-contracted carrier, but through our analysis is determined to be an ongoing provider.

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Billing

B. CPT Codes

Cytogenetics

Fluorescence in situ Hybridization (FISH)

Code Procedure

88271 DNA probe each

88275 Analysis 100-300 interphase cells

88291 Interpretation and report

Chromosomal G-Banding

Code Procedure

88237 Tissue Culture

88262 Analyze 15-20 cells, 2 karyotypes, w/ banding

88280 Additional karyotypes, each study

88291 Interpretation & Report

UroVysion®

Code Procedure

88120 Cytopathology in situ hybridization, urinary tract specimen with morphometric analysis, 3-5 probes, manual

88121 Using computer assisted technology

Cytology

Code Procedure

88173 Cyto FNA, Interpretation

88104 Cyto Non-Gyn Smears

88112 ThinPrep, Non-Gyn Fluids

88108 CytoSpin, Non-Gyn Conc Tech

88162 Extensive study (6 or more slides)

88305 Cell Block

88312 Special Stain, Group 1 (microorganisms)

88313 Special Stain, Group 2

88342 IHC, each Antibody

88360 IHC Quant, each Antibody

85097 Bone Marrow Smear Interpretation

85060 Peripheral Blood Smear Interpretation

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Billing

B. CPT Codes

Flow Cytometry

Codes Antibody

88184 Individual Antibodies, First Antibody

88185 Individual Antibodies, Each Additional Antibody

Codes Interpretation

88187 Flow interpretation, 2-8 markers

88188 Flow interpretation, 9-15 markers

88189 Flow interpretation, 16 or more markers

Histology

Code Procedure

88302 Surgical Lev 2, Gross & Micro





88311 Decal

88312 Special Stain, Group 1 (microorganisms)

88313 Special Stain, Group 2

88314 Special Stain on Frozen Section

88329 Path Consult During Surgery

88321 Consult

88331 Frozen Section, first block

88332 Frozen Section, additional tissue block

88333 Touch prep Introperative Cyto Exam

88334 Touch prep Introperative Cyto Exam Additional

88342 IHC, each Antibody

88360 IHC Quant, each Antibody

88365 Tissue ISH, each probe

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Billing

B. CPT Codes

Molecular

Code Molecular Test

81206 BCR/ABL1 (t9;22) (qualitative or quantitative)

81207 BCR/ABL1 other breakpoint (qualitative or quantitative)

81208 BCR/ABL1 minor breakpoint (qualitative or quantitative)

81210 BRAF(v-raf murine sarcoma viral onogene homolog B1), gene analysis, V600E variant

81245 FLT3 gene analysis, internal tandem duplication (ITD) variants

81261 IGH, gene rearrangement analysis to detect abnormal clonal populations; amplified methodology (B-cell clonality)

81263 IGHV, variable region somatic mutation analysis

81270 JAK2 gene analysis, p. Val617Phe (V617F) variant

81275 KRAS gene analysis, variants in codons 12 and 13

81310 NPM1 (nucleophosmin) gene analysis, exon 12 variants

81340 Tcell antigen receptor; beta

81342 Tcell antigen receptor; gamma

81402 cKit (D816)

81402 MPL515/505

81403 ABL1 variants in the kinase domain

81403 CEBPA, Molecular Pathology procedure Level 4

81403 JAK2 Exon12

81404 cKit (AML)

81404 TP53 full gene sequence or targeted sequence analysis of >5 exons

81479 NOTCH 1

81235 EGFR

81479 MatBA® - CLL

81479 MatBA® - SLL

81479 MatBA® - DLBCL

81479 MatBA® - MCL

81479 UroGenRATM - Kidney

Cancer Genetics, Inc. uses CPT for the purpose of establishing a system through which to obtain payment for our services. These codes serve as an indicator and are only to be used as a reference. This information is valid as of 2013.

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Reporting

A. Accessing Patient Reports

We offer our clients standard methods of communication such as email or fax to HIPAA compliant machines, as well as through the U.S. postal service. Alternatively, we offer HIPPA compliant, web-based report system through which reports can be accessed at anytime and anywhere. We maintain extended office hours so that a qualified member of our staff is always available to send the information to you when you need it.

CGI Reports: Access Patient Reports Instantly

This service offers clients access to their own patients’ reports through our interactive website. Each client is given an individual username and password that allows them to gain access their patients’ reports and communicate with our client services staff. This web-based, secure structure puts all of your patients’ reports right at your fingertips. Clients have the capability to access and view reports from the office, at home, or on the go. All CGI Reports are generated by our pathologist and can be viewed by logging in at https://cgireports.com. Please call our office at 888-334-4988 to be set up with CGI Reports.

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Once you have logged in you will be taken to the home screen. From here, you can choose to review reports, follow case logs, and view/respond to comments.

CGI Reports Login Page

Accessible from www.cancergenetics.com

https://cgireports.com/

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Reporting

A. Accessing Patient Reports

John Doe The best doctor John Doe The best doctor John Doe The best doctor

John Doe The best doctor















John Do The best doctor

e The best doctor

Convenient

Menu Access








Real-time status of each case

Convenient menu access

Easily assessable report in PDF format

Abnormal cases are highlighted in red

Real-time processing status of each case

Customizable CGI Reports table

5 CGI Reports Home Page

From the “My Reports” page, you can perform the following:

follow the status of each case

organize the report table per your needs

access patient reports in PDF format

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Reporting

B. Laboratory Reports

SummationTM Reports: An All-Inclusive Diagnostic/Prognostic Summary

Summation

TM is a CGI-developed comprehensive one page,

one view color diagnostic summary report. By choosing Summation

TM, our hematopathologists will work up a patient’s

case based on the clinical information and diagnosis provided. Our Summation

TM report integrates IHC, flow cytometry, cytogenetics, FISH and molecular genetic

test results into a concise and clinically relevant summary that: • Provides comprehensive diagnostic information, • Utilizes user-friendly and easy to interpret format, and • Offers appropriate patient management information.

The integration of all CGI’s testing technologies into a Summation

TM report drives quick decisions by

enabling clinicians/physicians to efficiently arrive at a definitive diagnosis. Our integrative Complete

SM Programs are reported as a Summation

TM report.

Please see our Sample Report booklet for an example of a SummationTM

Report and sample reports.

CGI CompleteSM: An integrative test system for CLL and DLBCL risk-stratification.

CGI Laboratories is a Center of Excellence for the management of Chronic Lymphocytic Leukemia (CLL) and Diffuse Large B-cell Lymphoma (DLBCL) by servicing world-class and proprietary assays. Complete

SM integrates the latest

prognostic molecular markers to risk-stratify individual patients for disease progression, response to treatment, and overall prognosis.

CLL CompleteSM Tests DLBCL CompleteSM Tests

MatBA®-CLL/SLL Array CGH

IGHV Mutation Analysis TP53 Mutation Analysis NOTCH1 Mutation Analysis SF3B1 Mutation Analysis ZAP-70 & CD38 by Flow FISH Karyotyping

MatBA®-DLBCL Array CGH

SETRATM* TP53 Mutation Analysis B-Cell Clonality GCB vs. Non-GCB Subtyping by IHC FISH Karyotyping

*SETRATM

: Six Gene Expression Treatment Response Assay

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A. Quality Control Program

CGI is committed to providing reliable and accurate diagnostic services to our clients. Patient safety, in the form of accurate specimen identification, timely communication of life-altering diagnoses is paramount in everything we do. We monitor and improve our performance through a variety of methods, including performance improvement indicators, proficiency testing, external audits, and satisfaction surveys.

All quality concerns and incidents are subject to root cause analysis, and our procedures are all put through periodic evaluation via the Plan-Do-Check-Act model of continuous improvement, to ensure that we are providing the best services possible to our patients and clients. Protection of patient results from misuse or poor access is imperative and thus electronic and paper results are strictly guarded via password-protection and ID cards according to HIPPA guidelines.

CGI’s laboratory is GCP and HIPAA compliant, CLIA certified, CAP accredited, and holds licensure in several US States including New York State.

Our commitment to quality extends to our employees as we have a comprehensive safety program to ensure the health and well-being of everyone at CGI.

B. Licenses and Credentials

CGI and CGI Laboratories are fully approved, accredited and licensed by CLIA, CAP, Medicare/Medicaid and states of Florida, Maryland, New Jersey, New York, and Pennsylvania. Our operations extend throughout the East Coast and include multiple states in New England, Mid-Atlantic and the South. The laboratory operations adhere to HIPAA guidelines and policies.

Licenses can be printed directly from the Lab Services tab on our website at www.cancergenetics.com/laboratory-services/regulatory-licensing

CAP Accreditation Lab Number: 7191582, AU-ID: 1434060

CLIA Certificate Certificate Number: 31D1038733

Florida License 800018142

Maryland License 1395

New Jersey License 16864

Pennsylvania License 031978

New York License PFI: 8192

National Provider Number 1215980610

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C. Confidentiality

Permitted Uses and Disclosures of Protected Health Information (PHI)

CGI policy requires that the identity of anyone who requests access to Protected Health Information (PHI) will be verified before any disclosure of PHI is made. CGI will make reasonable efforts to use or disclose only the “minimum amount of confidential information necessary” in all circumstances.

Exceptions to the minimum necessary rule are:

PHI requested for treatment purposes

PHI provided to the patient or authorized by the patient, and/or

PHI requested as required by law for HIPAA compliance

Authorized Uses and Disclosures of Protected Health Information (PHI)

According to HIPAA regulation, CGI must obtain the individual’s written authorization for any use or disclosure of PHI that is not for treatment, payment, health care operations or other functions listed above as permitted uses and disclosures. An authorization must be written in plain language and contain specific information regarding the information to be disclosed or used, the person(s) disclosing and receiving the information, expiration, right to revoke in writing, signature of patient and date. In compliance with state law and regulation, CGI will document and retain the signed authorization in the patient’s folder. Patient will be provided with a copy of the same.

Patients have the right to revoke authorizations for release of records. The revocation should be in writing via a letter to CGI. The revocation will not affect any actions already taken by CGI based upon the original authorization.

Physical Safeguards of PHI

It is the policy of CGI that physical safeguards will be in place to reasonably ensure that PHI will not intentionally or unintentionally be disclosed in violation of the HIPAA regulation. These safeguards include physical and administrative protection of the PHI. This protection will also be extended to oral communication of PHI.

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D. Compliance Statement

It is CGI’s goal to meet or exceed all guidelines and regulations set forth for the operation of a clinical and research laboratory. As such, current and future policies and procedures must be created within the guidelines of all appropriate regulatory agencies.

1. It is CGI’s policy to adhere to current CAP Terms of Accreditation, as well as all applicable federal, state, and local regulations.

2. Each Section Supervisor is responsible for periodically reviewing regulations relevant to his/her discipline for each state in which CGI offers testing. Any regulatory changes should be discussed in order to determine appropriate action by the laboratory.

3. The laboratory will abide by the privacy and information protection regulations set forth by the HIPAA.

4. The laboratory directors will notify CAP whenever the laboratory is investigated by a state or federal agency or for adverse media attention related to the laboratory performance. Notification must occur no later than 2 working days after the laboratory learns of an investigation or adverse media attention.

5. The laboratory directors will notify CAP when there is a change in the laboratory’s test menu. Notification must occur prior to starting new patient testing.

6. The laboratory directors will notify CAP of changes in location, ownership or directorship of the laboratory. Notification must occur prior to the change(s); or, in the case of unexpected changes, no later than 2 working days afterwards.

7. The lab participates in all relevant CAP surveys and the New York State proficiency testing program.

8. CAP checklists will be reviewed annually. A Self-Evaluation will be conducted in the interim year between CAP inspections, and a completed Verification Form will be submitted to CAP.

9. The laboratory director will notify all states in which it offers testing and CAP in the event that the laboratory should cease operation, and where records will be available in accordance with the Record Retention & Disposal Policy.

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CGI Expand Dx™

CGI Expand Dx™ is an initiative offered by CGI for the expansion of pathology services through a joint collaboration with CGI laboratories™. The program is designed to enhance and expand your pathology services in cancer diagnostics and personalized cancer treatment by developing your outreach to the hospital

community and enhancing your local partnerships. CGI Expand Dx™’s APS system works to build on your laboratory’s capabilities to increase efficiency and drive revenue to help you stay competitive and grow in today’s evolving market.

To learn more visit www.cgiexpanddx.com or contact us at [email protected].

CONNECT

CGI Laboratories’ team performs an onsite evaluation of your pathology laboratory operations.

EXPAND

By expanding your test menu and reaching out to new clientele, CGI Expand Dx™ program enables you to improve patient value.

GROW

The CGI Expand Dx™ team offers key benefits to allow your hospital outreach program to grow.

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CGI Expand Dx™

Test Menu

CYTOGENETICS G-Banding Fluorescence In-Situ Hybridization (FISH) Acute Lymphocytic Leukemia (ALL) B-ALL PEDIATRIC/ADULT

11q23 (MLL-Break Apart) t(9;22) (BCR/ABL/ASS) 17p13 (TP53) t(12;21) (ETV6/RUNX1) 9p21 (p16/CDKN2A) CEP4, 10, 17

T-ALL 14q11 (TCR-Alfa/Delta Break Apart)

Acute Myeloid Leukemia (AML) 11q23 (MLL-Break Apart) t(8;21) (ETO/AML1) [M2] t(15;17) (PML/RARA) [M3] inv(16) (CBFB-Break Apart) [M4, Eos]

Anaplastic Large Cell Lymphoma (ALCL) 2p23 (ALK-Break Apart)

Chronic Lymphocytic Leukemia (CLL) 11q22.3 (ATM)/17p13 (TP53) CEP12/13q14/13q34 CEP6/6q23 (c-MYB) t(11;14)(CCND1/IGH)

Chronic Myelogenous Leukemia (CML) t(9;22) (BCR/ABL/ASS)

CML in blast crisis t(9;22) (BCR/ABL/ASS) 17p13 (TP53) CEP8

Multiple Myeloma (MM) with purified plasma cells (PPC)

13q14/13q34 17p13 (TP53) 1p/1q D5S23/D5S72/CEP9/CEP15 t(4;14) (FGFR3/IGH) t(11;14) (CCND1/IGH) t(14;16) (lGH/MAF) Also Available : IGH-Break Apart CEP7/CEP11 t(6;14) (CCND3/IGH) t(14;20) (IGH/MAFB)

Myelodysplastic Syndrome (MDS) 5p15.2/5q31 CEP7/7q31 CEP8 20q12 11q23 (MLL-Break Apart)

Myeloproliferative Disease (MPD) 4q12 (FIP1L1/CHIC2/PDGFRA) 5q33 (PDGFRB-Break Apart) BCR/ABL (BCR/ABL/ASS) CEP8/CEP9

Non-Hodgkin’s Lymphoma (NHL) Burkitt: t(8;14) (MYC/IGH) DLBCL: 3q27 (BCL6-Break Apart) Follicular: t(14;18) (IGH/BCL2) Mantle: t(11;14) (CCND1/IGH) MALT Lymphoma: MALT1-Break Apart

Non-Hodgkin’s Lymphoma (NHL) Also Available: IGH-Break Apart c-MYC-Break Apart

BM Transplant Monitoring CEP X/Y

FISH for Solid Tumors ALK-Break Apart (NSCLC) PathVysion

® (HER2/neu) (Breast)

UroVysion® (Bladder)

ANATOMIC PATHOLOGY (see pg. 45) FLOW CYTOMETRY (see pg. 45) Lymphoid Myeloid/Lymphoid/Acute Leukemia Paroxysmal Nocturnal Hemoglobinuria (PNH) Plasma Cell Neoplasms ZAP-70 MOLECULAR DIAGNOSTICS Acute Myeloid Leukemia (AML)

CEBPA mutation c-KIT mutation (Exon 8 and 17) FLT3 mutation (ITD, D835) NPM1 mutation (Exon 12)

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)


IGHV mutation NOTCH1 mutation TP53 mutation SF3B1 mutation

Chronic Myeloid Leukemia (CML) ABL kinase domain mutation BCR-ABL (PCR) quantitative

Major (p210) (IS) - Minor (p190) BCR-ABL (PCR) qualitative

Major (p210) - Minor (p190) Lymphoma

B-Cell Clonality (IGH)

T-Cell Clonality (TCR) T-Cell Clonality (TCRβ)

Non-CML Myeloproliferative Neoplasms (MPN) c-KIT mutation (systemic mastocytosis) (D816) JAK2 V617F mutation

Reflex to MPL515/505 Reflex to JAK2 Exon 12

JAK2 Exon 12 mutation MPL515/505 mutation

Solid Tumor KRAS mutation (CRC, NSCLC) BRAF mutation (CRC) EGFR mutation (NSCLC) NRAS mutation (CRC, Melanoma, Thyroid cancer) UroGenRA

TM-Kidney Array CGH (Diagnosis – Subtype)

CLL COMPLETE

SM


IGHV mutation TP53 mutation NOTCH1 mutation SF3B1 mutation

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CLL COMPLETESM


IGHV mutation TP53 mutation NOTCH1 mutation SF3B1 mutation ZAP-70 (flow) CD38 (flow) Karyotype/FISH

DLBCL COMPLETESM

MatBA®-DLBCL Array CGH

SETRATM

(Six Gene Expression Treatment Response Assay

TP53 Mutation Analysis B-Cell Clonality GCB vs. Non-GCB Subtyping Karyotype/FISH

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CGI Expand Dx™

ANATOMIC PATHOLOGY

FLOW CYTOMETRY

Lymphoid Panel CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11c, CD19, CD20, CD23, CD38, CD45, CD56, CD57, Kappa, Lambda

Myeloid/Lymphoid/Acute Leukemia Panel CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11b, CD11c,CD13, CD14, CD15,CD16 CD19, CD20, CD22, CD23, CD33, CD34, CD38, CD45, CD56, CD57, CD64, CD71, CD117, HLA-DR, Kappa, Lambda,

Paroxysmal Nocturnal Hemoglobinuria (PNH) Panel CD14, CD16, CD45, CD55, CD59, CD235a (Glycophorin A), FLAER

Plasma Panel CD4, CD8, CD3, CD7, CD10, CD19, CD20, CD28, CD34, CD38, CD45, CD56, CD117, CD138, sKappa, sLambda, cKappa, cLambda, cIgM, cIgA, cIgG

Zap-70 Panel CD3, CD5, CD19, ZAP-70, CD45

Also Available: MPO, TdT, CD1a, CD79a, CD25, CD41, CD43, CD61, CD103, FMC7

7 IHC

SMA (Actin, Smooth Muscle)

CD30

DOG1

Lambda

PMS2

MSA (Actin, Muscle Specific)

CD31

E-cadherin

Lysozyme

P.carinii (Pneumocystis Carinii)

ALK1

CD33

EGFR (Epidermal Growth Factor Receptor)

Mammaglobin

Podoplanin (D2-40)

Annexin A1

CD34

EMA (Epithelial Membrane Antigen)

MART-1/melan A

PR (Progesterone Receptor)

Basal Cell Cocktail (34BE12 + p63)

CD43

Ep-CAM (Epithelial Specific Antigen)

Melanosome (HMB-45)

PSA (Prostate Specific Antigen)

bcl-2

CD45 (LCA)

Epithelial Related Antigen (moc31)

Mesothelin

PSAP (Prostatic Acid Phosphatase)

bcl-6

CD45RO

EBV (Epstein-Barr Virus) LMP

MLH1

RCC (Renal Cell Carcinoma)

BOB.1

CD56

ER (Estrogen Receptor)

MSH2

S100

c-KIT (CD117)

CD57

Factor VIII Related Antigen

MSH6

SOX-2

CA 19-9

CD61

Factor XIIIa

MUM1

Synaptophysin

CA 125

CD68

Fascin

MBP (Myelin Basic Protein)

TAG-72

Calcitonin

CD79a

Fli-1

Myeloperoxidase (MPO)

TdT (Terminal Deoxynucleotidyl Transferase)

Caldesmon

CD99

GCDFP-15

Myogenin

Thyroglobulin

Calponin-1

CD138 (Syndecan-1)

GFAP (Glial Fibrillary Acidic Protein)

Myoglobin

Toxoplasma (Toxo)

Calretinin

CD163

Glycophorin A

Myosin, Smooth Muscle (heavy chain)

TTF-1 (Thyroid Transcription Factor-1)

CEA (Carcinoembryonic Antigen)

CDX-2

Granzyme B

Napsin A

TRAcP (Tartrate-Resistant Acid Phosphatase)

CD1a

Chromogranin A

Helicobacter pylori

Neurofilament

Tryptase

CD2

Cytomegalovirus (CMV)

HepPar-1 (HSA)

NSE (Neuron Specific Enolase)

Tyrosinase

CD3

COX-2 (Cyclooxygenase 2)

HER-2/neu, PATHWAY

Oct2

Villin

CD4

Cyclin D1

HHV-8 (Human Herpes Virus Type 8)

Oct4

Vimentin

CD5

Cytokeratin 903

HSV I&II

p16

WT1

CD7

Cytokeratin (CAM 5.2)

hCG (Human Chorionic Gonadotropin)

p27kip1

ISH

CD8

Cytokeratin (Pan) AE1/AE3

hGH (Human Growth Hormone )

p53

EBER

CD10

Cytokeratin 17

IgA (Immunoglobulin A)

p57kip2

Kappa

CD14

Cytokeratin 19

IgD (Immunoglobulin D)

p63

Lambda

CD15

Cytokeratin 20

IgG (Immunoglobulin G)

PTH (Parathyroid Hormone )

CD20

Cytokeratin 5/6

IgM (Immunoglobulin M)

PAROVIRUS B19

CD21

Cytokeratin 7

Inhibin

PAX2

CD22

Cytokeratin 8

Insulin

PAX5

CD23

Cytokeratin 8 &18

Kappa

PAX8

CD25

Desmin

Ki-67

PLAP (Placental like Alkaline Phosphatase)

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CGI Select One™

CGI’s Select One™ program offers unique solutions to investigators, CROs, and biopharma companies in support of their Phase 1-3 clinical trial testing needs. As a leader in personalized oncology, CGI provides disease-specific biomarker knowledge, proprietary assays, and state of the art oncology laboratory services. We believe the integration of clinical information with drug discovery is critical to

providing customized solutions for patient stratification and treatment. Below is an overview of our services:

Customizable tests and techniques to improve clinical trial design

Time sensitive trial test development

Rapid proof-of-concept studies

Dependable results from early phase initiatives

Microarrays to provide enhanced genomic information

Enhanced understanding of complex diseases at earlier stages

Our clinical team is backed by CGI’s strong R&D background, which has led to the development of innovative and proprietary testing along with an in-depth understanding of complex cancer states. We leverage this knowledge and experience in oncology-based testing to provide solutions that lead to effective patient stratification, increased responder population, endpoints validation and optimization.

The size of our company enables us to respond quickly to the needs of clients and provide them with high quality specialized outcomes for clinical trials. Our laboratory, which is GCP and HIPAA compliant, CLIA certified and CAP accredited ensures the service we provide to clients is accurate and reliable. Through our focus and dedication to innovation and personalized oncology, clients also benefit from our:

World-class expertise in oncology

Strong oncology-focused R&D program

Experience developing custom DNA probe panels and microarrays

Adaptability and quick response to client needs

Renown Scientific Advisory Board

For more information please contact us at [email protected] or visit our website http://cancergenetics.com/laboratory-services/selectone/.

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Documents

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