finding cancer genes
TRANSCRIPT
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
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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