Finding Cancer Genes

Finding Cancer Genes

Finding Cancer Genes

• CML: Chronic Myelogenous Leukemia

– Asymptomatic at time of diagnosis• Abnormal white blood cell count• Stable for 3 – 5 years followed by “Blast Crisis”• Fatal within 3 – 6 months of Blast crisis

• 20% of all leukemia's• 5000 cases per year in US (compare with 180,000 lung

cancer cases)

Finding Cancer Genes

• CML: Chronic Myelogenous Leukemia

– All CML cells harbor Philadelphia chromosome

• 1960:• Peter Nowell • David Hungerford

• Nowell P, Hungerford D. "A minute chromosome in chronic granulocytic leukemia." Science 1960;132:1497.

Finding Cancer Genes

• 1973:• Janet D. Rowley

• Discovered t(9;22)

• Rowley JD. "A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining [letter]". Nature 1973;243:290–3.

Finding Cancer Genes

Finding Cancer Genes

Finding Cancer Genes

Finding Cancer Genes

Finding Cancer Genes

Bcr-Abl

Non-physiological Activation of Bcr-Abl Activation of Signaling

c-Abl – Physiological Roles

• c-Abl is a nuclear-shuttling protein that regulates p53

c-Abl – Physiological Roles

c-Abl Kinase Domain Structure

STI-571

STI-571

STI-571

www.cmlsupport.com

Parametric Linkage analysis

3

Fig. 1. The β-catenin protein interaction network.

Michael B. Major et al. Science 2007;316:1043-1046

Published by AAAS

Fig. 3. WTX promotes β-catenin ubiquitination and degradation.

Michael B. Major et al. Science 2007;316:1043-1046

Published by AAAS

Tumour Suppressors

•Example 4: REST

Thomas F. Westbrook , Eric S. Martin , Michael R. Schlabach , Yumei Leng , Anthony C. Liang , Bin Feng , Jean J. ...

A Genetic Screen for Candidate Tumor Suppressors Identifies REST

Cell, Volume 121, Issue 6, 2005, 837 - 848