Patient Test Results

Clinically Relevant Genomic Alterations Detected

TIER 2: VARIANTS OF POTENTIAL CLINICAL SIGNIFICANCE

Predictive Variants

MSI Result

I MSI-H Not detected

Comments

TP53 mutations may increase resistance to ionizing radiation therapy (El-Deiry, 2003, Miyasaka et al., 2015). Metformin has been shown to improve response to radiation in cells harboring TP53 disruptive mutations and decrease regional recurrence (Skinner et al., 2012).

: Rana Bu-Ajram: 09/10/1972: Female: 06/03/2019 : 06/04/2019

Physician Name : Dr. Faruq

: Eastern Biotech & Life Sciences : 19023175: Peripheral blood: Ovarian serous carcinoma

Hospital Name Report ID SpecimenHistory

Patient Name DOBGender Test Ordered Date Report Date

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2. Detailed Biomarker Information

2.1. TP53-G266R (p.Gly266Arg)

TIER 2: Variant of Potential Clinical Significance

2.1.1 BIOMARKER RESULTS SUMMARY Marker Result Summary

TP53 - MUTN (seq):p.Glv266Arq (G266R)

TP53-G266R is an inactivating mutation.

Clinical relevance TP53 is a tumor suppressor that encodes the p53 protein; alterations in TP53 may result in a loss of p53 function, yet an increase in the expression and stability of the mutant p53 protein in the nucleus, sometimes leading to oncogenic effects, including genomic instability and excessive cell proliferation (Levine, 1997; 9039259, Wang et al., 2005; 15625370, Koga et al., 2001; 11400116, Kato et al., 2003; 12826609, Houben et al., 2011; 21760960, Olivier et al., 2009; 18802452). At present, there are no approved therapies targeting TP53 alterations, despite their high prevalence in cancer. Therapeutic approaches under investigation include gene therapy for TP53 and (dendritic cell-based) TP53 vaccines (Schuler et al., 2014; 24583792, Vermeij et al., 2011; 21541192, Saito et al., 2014; 24982341). Tumors with TP53 mutations may be sensitive to the Weel inhibitor adavosertib (MK-1775), and clinical trials are currently underway for patients with solid tumors and hematologic malignancies (Hirai et al., 2010; 20107315, Bridges et al., 2011; 21799033). Aurora kinase A inhibitors are another therapeutic approach under investigation for TP53-mutated cancers (Vilgelm et al., 2015; 25398437, Li et al., 2015; 25512615, Katayama and Sen, 2011; 21761334, Tentler et al., 2015; 25758253, Kalous et al., 2013; 24091768).

2.1.2 BIOLOGICAL RELEVANCE of TP53-G266R (p.Gly266Arg)

Molecular function

Incidence in disease

TP53 alterations in Ovarian serous carcinoma

TP53 G266R is a missense alteration located within the DNA-binding domain (DBD) of the p53 protein Qoerger and Fersht, 2008; 18410249). DBD mutations are thought to result in loss of function via the loss of transactivation of p53- dependent genes (Kato et al., 2003; 12826609). TP53 G266R has been reported to result in substantially reduced transactivation capacity, as compared with wild-type TP53, in yeast assays (IARC TP53 Database, release R18) (Petitjean et al., 2007; 17311302, Kato et al., 2003; 12826609, Okada et al., 2006; 16827139).

TP53 mutations have been reported in 71 % (1039/1472) of Ovarian serous carcinoma samples analyzed in COSMIC Qan 2019). TP53 mutations have been reported in 71-96% of Ovarian serous carcinoma samples (cBioPortal for Cancer Genomics, Jan 2019). TP53 mutations have been reported to be particularly prevalent in high-grade serous carcinoma (HGSC), with an incidence of 94-99% (Cancer Genome Atlas Research Network 2011; 21720365, Seagle et al., 2015; 26215675, Ahmed et al., 2010; 20229506, Goranova et al., 2017; 28359078, Kobel et al., 2016; 27840695). In a study of 57 low-grade ovarian serous carcinoma and 19 ovarian serous borderline tumors, no TP53 mutations were identified (Hunter et al., 2015; 26506417).

2.1.3 CLINICAL RELEVANCE of TP53-G266R (p.Gly266Arg)

Role in disease

TP53 alterations in Ovarian serous carcinoma

Loss of tumor suppressor p53, which is encoded by the TP53 gene, is common in aggressive advanced cancers (Brown et al., 2009; 19935675). Carriers of a germline mutation in TP53 have Li-Fraumeni Syndrome, an inherited cancer syndrome resulting in multiple tumors in early adulthood, including breast cancer, brain tumors, and leukemias (Malkin et al., 1990; 1978757, Srivastava et al., 1991; 2259385, Santibafiez-Koref et al., 1991; 1683921). Expression of p53 in normal cells is low; however, TP53 alterations, including those that result in loss of p53 tumor suppressor function, may lead to stabilization and increased expression of p53, particularly in the nucleus, and several studies have shown that it may have oncogenic gain-of-function effects (Wang et al., 2005; 15625370, Koga et al., 2001; 11400116, Kato et al., 2003; 12826609, Houben et al., 2011; 21760960, Olivier et al., 2009; 18802452). Studies have reported

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Phase I Data

Preclinical

TP53 alterations in Ovarian serous carcinoma

A Phase 1 trial of SGT-53 in 11 patients with refractory cancer reported that the gene therapy complex was well tolerated with stable disease achieved in seven patients at six weeks and a median survival of 340 days; in addition, one tumor which was previously classified as inoperable was able to be resected (Senzer et al., 2013; 23609015). A Phase 1 trial of SGT-53 in combination with docetaxel in 14 patients with advanced cancer has reported three partial responses and two stable diseases per RECIST; this combination was well tolerated (Pirollo et al., 2016; 27357628).

APR-246 has been reported to restore the sensitivity of resistant TP53-mutant ovarian carcinoma clinical samples and cell lines to cisplatin and doxorubicin (Mohell et al., 2015; 26086967, Fransson et al., 2016; 27179933). A preclinical study reported that treatment of breast cancer, non-small cell lung cancer, and glioblastoma mouse models with SGT-53 resulted in sensitivity to anti-PDl antibodies; the combination therapy resulted in greater activation of tumor infiltrating lymphocytes and synergistic tumor growth inhibition as compared with either treatment alone (Kim et al., 2018; 3028834 7).

2.1.5 SAMPLE RELEVANT THERAPIES

Therapies targeting TP53

Drug Trade Name Level of Evidence

Target/Rationale Highest Level of Clinical Development

SGT-53 D TP53 gene therapy Phase 1 (Solid Tumor) delivered via Phase 2 (Glioblastoma, Glioma, Pancreatic carcinoma) transferrin-targeted nanonarticles.

APR-246 None Reactivates mutant p53. Phase 2 (Ovarian serous carcinoma) found Phase 2 (Melanoma, Gastroesophageal junction

carcinoma, Esophaqeal carcinoma)

ALT-801 None p53-targeted T-cell Phase 1 (Solid Tumor) found receptor-IL2 fusion. Phase 2 (Melanoma, Urothelial carcinoma, Bladder

carcinoma, Urethral melanoma, Urethral carcinoma, Multiple mveloma (MM))

COTI-2 None Reactivates mutant p53. Phase 1 (Ovarian carcinoma) found Phase 1 (Endometrial carcinoma, Head and neck

sauamous cell carcinoma (HNSCC), Cervical carcinoma)

Therapies targeting Aurora kinase A

Drug Trade Name Level of Target/Rationale Highest Level of Clinical Development Evidence

Alisertib D Aurora A small molecule Phase 2 (Ovarian carcinoma) kinase inhibitor. Phase 3 (Perinheral T-cell lvmnhoma (PTCL))

ENMD-2076 D Aurora A small molecule Phase 2 (Ovarian carcinoma) kinase inhibitor. Phase 2 (Fibrolamellar hepatocellular carcinoma, Breast

carcinoma, Fallopian tube adenocarcinoma, Soft tissue sarcoma)

AT9283 None Aurora A, B, Jak2, Jak3, Phase 1 (Solid Tumor) found Bcr-Abl kinase inhibitor. Phase 2 (Acute myelocytic leukemia (AML), Multiple

myeloma (MM), Chronic myelocytic leukemia (CML), Acute lvmphocvtic leukemia (ALL))

AMG 900 None Aurora A, B, C small Phase 1 (Solid Tumor) found molecule kinase Phase 1 (Acute myelocytic leukemia (AML))

inhibitor.

SNS-314 None Aurora A, B small Phase 1 (Solid Tumor) found molecule kinase

inhibitor.

TAS-119 None Selective Aurora A Phase 1 (Solid Tumor) found kinase inhibitor.

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Markers Trial ID Title Phase Tar ets Locations/contact

4 TP53 NCT03579316 Adavosertib With or Without Phase 2 PARP, •Overall contact: Robert Coleman,

Olaparib in Treating WEEl rcoleman@mdanderson.org, 713-

Participants With Recurrent 745-3357

Ovarian, Primary Peritoneal, or • M D Anderson Cancer Center:Texas, USA, Robert L. Coleman,

Fallopian Tube Cancer (TX)

• Dana Farber Cancer Institute:Massachusetts, USA, (MA)

5 TP53 NCT02134067 Dose-escalating, Safety, Phase 1 Aurora •Overall contact: Takekazu Aoyama,

Tolerability and PK Study of kinase A MD, PhD, aoyama@taihopui.com,

TAS-119 in Combination With 609-750-5331

Paclitaxel in Patients With • University of Colorado Hospital

Advanced Solid Tumors Anschutz Cancer Pavilion:Colorado, USA, (CO)

•Washington University School ofMedicine Division of OncologySiteman Cancer Center: Missouri,USA, (MO)

• Memorial Sloan-Kettering CancerCenter: New York, USA, (NY)

•Vanderbilt Ingram Cancer Center:Tennessee, USA, (TN)

*Note: the trials listed above were matched to the biomarkers identified in this tumor; the list may not be comprehensive.

Trials Prioritized By Region*

Markers Trial ID Title Phase Tar ets Locations/contact

1 TP53 NCT02433626 Study of COTI-2 as Phase 1 TP53 •Overall contact: Richard Ho, MD-

Monotherapy or Combination PhD, rho@cotingapharma.com,

Therapy for the Treatment of 519-858-515 7

Malignancies • MD Anderson Cancer Center:Texas, USA, Shannon Westin, MD,(TX)

2 TP53 NCT02576444 OLAParib COmbinations Phase 2 AKT,ATR, •Overall contact: Manuel Avedissian,

MTOR, manuel.avedissian@yale.edu, 203-

mTORCl, 737-3669

mTORC2, •Yale Cancer Center: Connecticut,

PARP, USA, Alexandra Minnella, alexandra.minnella@yale.edu, (CT)

RPS6KB1, • Dana-Farber Cancer Institute:WEEl Massachusetts, USA, Loan Vuong,

loan_ vuong@dfci.harvard.edu, (MA) •Vanderbilt-Ingram Cancer Center:Tennessee, USA, Tom Leonard-Martin, Thomas.Leonard-Martin@vumc.org, (TN)

•Cleveland Clinic Taussig CancerInstitute: Ohio, USA, NancyFrazier, frazien@ccf.orq, (OH)

3 TP53 NCT02659241 A Pilot Study of Induction Weel Early WEEl •Overall contact: Shannon Westin,

Inhibition in Ovarian Cancer Phase 1 MD, 713-794-4314• University of Texas MD AndersonCancer Center: Texas, USA, (TX)

4 TP53 NCT03579316 Adavosertib With or Without Phase 2 PARP, •Overall contact: Robert Coleman,

Olaparib in Treating WEEl rcoleman@mdanderson.org, 713-

Participants With Recurrent 745-3357

Ovarian, Primary Peritoneal, or • M D Anderson Cancer Center:Texas, USA, Robert L. Coleman,

Fallopian Tube Cancer (TX)

• Dana Farber Cancer Institute:Massachusetts, USA, (MA)

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Hirai H, Arai T, Okada M, Nishibata T, Kobayashi M, Sakai N, Imagaki K, Ohtani J, et al. "MK-1775, a small molecule Weel

inhibitor, enhances anti-tumor efficacy of various DNA-damaging agents, including 5-fluorouracil." Cancer biology &

therapy 7 (2010): 514-22.

Houben R, Hesbacher S, Schmid C, Kauczok C, Flohr U, Haferkamp S, Miiller C, Schrama D, et al. "High-level expression of wild­

type p53 in melanoma cells is frequently associated with inactivity in p53 reporter gene assays." PloS one 7 (2011):

e22096.

Hunter S, Anglesio M, Ryland G, Sharma R, Chiew Y, Rowley S, Doyle M, Li J, et al. "Molecular profiling of low grade serous

ovarian tumours identifies novel candidate driver genes." Oncotarget 35 (2015): 37663-77.

Joerger A, Fersht A. "Structural biology of the tumor suppressor p53." Annual review of biochemistry (2008): 557-82.

Kalous 0, Conklin D, Desai A, Dering], Goldstein J, Ginther C, Anderson L, Lu M, et al. "AMG 900, pan-Aurora kinase inhibitor,

preferentially inhibits the proliferation of breast cancer cell lines with dysfunctional p53." Breast cancer research and

treatment 3 (2013): 397-408.

Katayama H, Sen S. "Functional significance of Aurora kinase A regulatory interactions with p53-ERa: complex in human breast

cancer cells." Hormones & cancer 2 (2011): 117-24.

Kato S, Han S, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C. "Understanding the function-structure and function-mutation

relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis." Proceedings of the

National Academy of Sciences of the United States of America 14 (2003): 8424-9.

Kim S, Harford], Moghe M, Rait A, Chang E. "Combination with SGT-53 overcomes tumor resistance to a checkpoint inhibitor."

Oncoimmunology 10 (2018): e1484982.

Koga T, Hashimoto S, Sugio K, Yoshino I, Nakagawa K, Yonemitsu Y, Sugimachi K, Sueishi K. "Heterogeneous distribution of P53

immunoreactivity in human lung adenocarcinoma correlates with MDM2 protein expression, rather than with P53 gene

mutation." International journal of cancer 4 (2001): 232-9.

KrimmelJ, Schmitt M, Harrell M, Agnew K, Kennedy S, Emond M, Loeb L, Swisher E, et al. "Ultra-deep sequencing detects

ovarian cancer cells in peritoneal fluid and reveals somatic TP53 mutations in noncancerous tissues." Proceedings of the

National Academy of Sciences of the United States of America 21 (2016): 6005-10.

Kobel M, Piskorz A, Lee S, Lui S, LePage C, Marass F, Rosenfeld N, Mes Masson A, et al. "Optimized p53 immunohistochemistry is

an accurate predictor of TP53 mutation in ovarian carcinoma." The journal of pathology. Clinical research 4 (2016): 24 7-

258.

Leijen S, van Geel R, Sonke G, de Jong D, Rosenberg E, Marchetti S, Pluim D, van Werkhoven E, et al. "Phase II Study of WEEl

Inhibitor AZDl 775 Plus Carboplatin in Patients With TP53-Mutated Ovarian Cancer Refractory or Resistant to First-Line

Therapy Within 3 Months." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 36

(2016): 4354-4361.

Levine A. "p53, the cellular gatekeeper for growth and division." Cell 3 (1997): 323-31.

Lheureux S, Tinker A, Clarke B, Ghatage P, Welch S, Weberpals J, Dhani N, Butler M, et al. "A Clinical and Molecular Phase II

Trial of Oral ENMD-2076 in Ovarian Clear Cell Carcinoma (OCCC): A Study of the Princess Margaret Phase II

Consortium." Clinical cancer research: an official journal of the American Association for Cancer Research 24 (2018):

6168-6174.

Li Z, Sun Y, Chen X, Squires J, Nowroozizadeh B, Liang C, Huang]. "p53 Mutation Directs AURKA Overexpression via miR-25 and

FBXW7 in Prostatic Small Cell Neuroendocrine Carcinoma." Molecular cancer research: MCR 3 (2015): 584-91.

Ma C, Janetka J, Piwnica-Worms H. "Death by releasing the breaks: CHKl inhibitors as cancer therapeutics." Trends in molecular

medicine 2 (2011): 88-96.

Malkin D, Li F, Strong L, FraumeniJ, Nelson C, Kim D, Kassel], Gryka M, et al. "Germ line p53 mutations in a familial syndrome of

breast cancer, sarcomas, and other neoplasms." Science (New York, N.Y.) 4985 (1990): 1233-8.

Marxer M, Ma H, Man W, Poon R. "p53 deficiency enhances mitotic arrest and slippage induced by pharmacological inhibition of

Aurora kinases." Oncogene 27 (2014): 3550-60.

Matulonis U, Lee J, Lasonde B, Tew W, Yehwalashet A, Matei D, Behbakht K, Grothusen ], et al. "ENMD-2076, an oral inhibitor of

angiogenic and proliferation kinases, has activity in recurrent, platinum resistant ovarian cancer." European journal of

cancer (Oxford, England: 1990) 1 (2013): 121-31.

Matulonis U, Sharma S, Ghamande S, Gordon M, Del Prete S, Ray-Coquard I, Kutarska E, Liu H, et al. "Phase II study of MLN8237

(alisertib) , an investigational Aurora A kinase inhibitor, in patients with platinum-resistant or -refractory epithelial

ovarian, fallopian tube, or primary peritoneal carcinoma." Gynecologic oncology 1 (2012): 63-9.

Miyasaka A, Oda K, Ikeda Y, Sone K, Fukuda T, Inaba K, Makii C, Enomoto A, et al. "PI3K/mTOR pathway inhibition overcomes

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(2015): 181-93. Wang Y, Lin R, Tan Y, Chen J, Chen C, Wang Y. "Wild-type p53 overexpression and its correlation with MDM2 and p14ARF

alterations: an alternative pathway to non-small-cell lung cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 1 (2005): 154-64.

Zhang M, Zhuang G, Sun X, Shen Y, Wang W, Li Q, Di W. "TP53 mutation-mediated genomic instability induces the evolution of chemoresistance and recurrence in epithelial ovarian cancer." Diagnostic pathology 1 (2017): 16.

NCCN. "NCCN Guidelines® are referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.1.2016, Breast Cancer V.1.2016, Central Nervous System Cancers V.1.2015, Gastric Cancer V.3.2015, Non-Small Cell Lung Cancer V.4.2016, Colon Cancer V.2.2016, Rectal Cancer V.1.2016, Melanoma V.2.2016, Neuroendocrine Tumors V.1.2015, Ovarian Cancer V.2.2015, Pancreatic Adenocarcinoma V.1.2016, Prostate CancerV.2.2016, and Uterine Neoplasms V.2.2016. © 2016 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org"

5. Definitions of Variant Tiers and Levels of Evidence

Tier 1: Variants of Strong Clinical Significance

Level A Predictive of response: Therapy is FDA-approved in this disease, based on the presence of this biomarker. Predictive of resistance: Biomarker is included in professional guidelines as providing resistance to therapy. Diagnostic: Biomarker is included in professional guidelines as pathognomonic (required for diagnosis; characteristic of a particular disease). Prognostic: Biomarker is included in professional guidelines for clinical decision-making; specifically, the molecular criteria is included in an acce ted, clinicall relevant ro nostic scorin s stem.

Level B Predictive of response: Strong evidence (well-powered studies, consensus from experts) that biomarker predicts sensitivity to therapy. Predictive of resistance: Well-powered studies with expert consensus or smaller studies repeatedly confirmed or reproduced by different groups that variant predicts resistance to therapy. Diagnostic: Well-powered studies with expert consensus or repeatedly reported in smaller studies with consistent results or reproduced by different groups indicating diagnostic relevance. These markers may be mentioned in professional guidelines, but are suggestive of, rather than conclusive for, a specific diagnosis. Prognostic: Well-powered studies with expert consensus or smaller studies repeatedly with consistent results or re roduced b different rou s indicatin ro nostic relevance.

Level B/C Predictive of response: Consensus from experts, but lacking well-powered studies that biomarker predicts sensitivity to therapy. Not a licable for dru resistance, ro nostic, or dia nostic levels of evidence.

Tier 2: Variants of Potential Clinical Significance

Level C Predictive of response: Therapy is FDA-approved for a different disease, based on the presence of this biomarker (C.1); or, criteria for a clinical trial or investigative therapies with some clinical evidence that the biomarker predicts sensitivity (C.2). Predictive of resistance: Preclinical data strongly suggests resistance; reported in clinical cases. Diagnostic: Small studies, diagnostic for a group of related cancers or variants that are supportive of a diagnosis along with other genomic variants. Pro nostic: Multi le small studies rovidin ro nostic relevance.

Level CJD Predictive of response: Case reports or small case series including exceptional responders that indicate sensitivity to therapy. Not a licable for dru resistance, ro nostic, or dia nostic levels of evidence.

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ABL1

AKT1

ALK

APC

AR

AR/D1A

ATM

BRAF

BRCA1

BRCA2

CDH1

CDKN2A

CSF1R

CTCF

CTNNB1

DNMT3A

EGFR

EP300

EPHA3

EPHAS

Mutations lnDels Amplifications Rearrangements MSI

(SNVs) (25 Genes) (CNVs) (3 Genesr

(73 Genes) (14 Genes)

ERBB2 KIT RB1 APC PTCH1 AR

ERBB4 KRAS ROS1 AR/D1A PTEN BRAF

EZH2 LIFR RUNX1 ATM RB1 BRCA1

FBXWl MAP2K1 SETD2 BRCA1 RUNX1 BRCA2

FGFR1 MAP3K1 SMAD2 BRCA2 SETD2 EGFR

FGFR2 MET SMAD4 CDH1 ERBB2

FGFR3 MLH1 SMARCA4 CDKN2A FGFR1

FLT3 MPL SMARCB1 CTCF FGFR2

GATA3 MTOR SMO EGFR FGFR3

GNA11 NAV3 SRC EP300 KIT

GNAQ NFE2L2 STK11 ERBB2 KRAS

GNAS NOTCH1 TP53 GATA3 MET

HNF1A NPM1 VHL HNF1A PDGFRA

HRAS NRAS KIT PIK3CA

IDH1 PDGFRA MET

IDH2 PIK3CA MLH1

JAK2 PIK3R1 MTOR

JAK3 PTCH1 NOTCH1

KDR PTEN NPM1

KEP1 PTPN11 PDGFRA

ALK

FGFR3

ROS1

BAT-25

BAT-26

NR-21

NR-24

MON0-27

*limited fusions covered

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Circulating tumor DNA (ctDNA) is tumor DNA circulating freely in the blood of a cancer patient. ctDNA originates from tumor cells and can be present in a wide range of cancers. ctDNA is a specific cancer biomarker that can be used for detecting, measuring, and tracking somatic mutations that may drive cancer. Genomic profiling of ctDNA, referred to as liquid biopsy, can help match individual patients to personalized target therapy, without having to repeat a biopsy of the tumor itself. liquiCORE Detect is a liquid biopsy test with a custom gene panel that provides coverage of NCCN guideline recommended sites for solid tumors. The test is capable of detecting somatic mutations including single nucleotide variants (SNVs), small insertions and deletions (Indels), copy number variations (CNV), gene fusions, and microsatellite instability (MSI).

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liqui CŌRE Detect

liquiCORE Detect test covers portions of 73 genes and other clinically relevant genomic loci (full list is available upon request from CORE Diagnostics). Not all regions are tested for all variant types. The test interrogates and reports single nucleotide variants (SNVs), small insertions and deletions (Indels), copy number amplifications (CNA), gene fusions, and microsatellite instability (MSI). Some large scale genomic rearrangements, such as inversions, are not tested. Not all regions of all genes are sequenced or reported. liquiCOREDetect is able to detect single nucleotide variants and small insertions and deletions with allele frequencies ≤ 0.1%. liquiCOREDetect is able to detect copy number amplifications with at least 4.5 copies, fusions with allele frequencies >0.5%, and MSI with tumor fractions ≥2%. Certain sample specific factors, such as low plasma volume or improper collection technique, may result in reduced sensitivity. MSI status is determined by 5 established MSI markers. Gene fusions are tested ALK, ROS1, and FGFR3. Copy number amplifications can be detected in all genes, but amplifications in some genes may not be clinically relevant and may not be reported. Copy number amplifications may also not be reported in samples with low tumor DNA percentage or low-grade amplifications. This test cannot predict origin of cancer.

A negative test result means that the laboratory did not identify a reportable variant in any of the tested genes. For most cases it may mean that there is no residual tumor left in the body, however for small portion of the patients it may mean that ctDNA level fell below the limit of detection of the liquiCORE Detect test, clinical relevance of which may not be significant.

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Disclaimer

DNA studies do not constitute a definitive test for any disease conditions in any tested individual. This assay provides information on somatic alterations (SNVs, Indels, CNV and rearrangements) present in the sample, as well as status of high and low microsatellite instability (MSI-H and MSI-L). No further comments are made on the samples with no findings for MSI-L/H status. Clinical decisions regarding care and treatment of customers should not be solely based on this test. How this information is used to guide customer care is the responsibility of the physician.

The test is designed to assist health care practitioners in providing additional clinical information. The information therein should not be relied upon as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. Medical knowledge develops rapidly and new evidence may emerge between the time information is developed to when it is published or read.

CORE Diagnostics provides this information on an "as is" basis, and makes no warranty, express or implied, regarding the information. CORE Diagnostics specifically disclaims any warranties of merchantability or fitness for a particular use or purpose. CORE Diagnostics assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of this information or for any errors or omissions.

The information herein is not continually updated and may not reflect the most recent evidence. The information addresses only the topics specifically identified therein and is not applicable to other interventions, diseases, or stages of diseases. This information does not mandate any particular course of medical care. Further, the information is not intended to substitute for the independent professional judgment of the treating physician, as the information does not account for individual variation among customers.This is a transcribed report and the test was performed at the laboratory OSL 33.

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