finding cancer genes
TRANSCRIPT
![Page 1: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/1.jpg)
Finding Cancer Genes
![Page 2: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/2.jpg)
![Page 3: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/3.jpg)
![Page 4: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/4.jpg)
![Page 5: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/5.jpg)
![Page 6: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/6.jpg)
![Page 7: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/7.jpg)
![Page 8: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/8.jpg)
![Page 9: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/9.jpg)
![Page 10: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/10.jpg)
![Page 11: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/11.jpg)
![Page 12: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/12.jpg)
![Page 13: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/13.jpg)
![Page 14: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/14.jpg)
![Page 15: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/15.jpg)
![Page 16: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/16.jpg)
![Page 17: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/17.jpg)
![Page 18: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/18.jpg)
![Page 19: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/19.jpg)
![Page 20: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/20.jpg)
![Page 21: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/21.jpg)
![Page 22: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/22.jpg)
![Page 23: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/23.jpg)
![Page 24: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/24.jpg)
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)
![Page 25: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/25.jpg)
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.
![Page 26: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/26.jpg)
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.
![Page 27: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/27.jpg)
Finding Cancer Genes
![Page 28: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/28.jpg)
Finding Cancer Genes
![Page 29: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/29.jpg)
Finding Cancer Genes
![Page 30: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/30.jpg)
Finding Cancer Genes
![Page 31: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/31.jpg)
Finding Cancer Genes
![Page 32: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/32.jpg)
Bcr-Abl
![Page 33: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/33.jpg)
Non-physiological Activation of Bcr-Abl Activation of Signaling
![Page 34: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/34.jpg)
c-Abl – Physiological Roles
• c-Abl is a nuclear-shuttling protein that regulates p53
![Page 35: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/35.jpg)
c-Abl – Physiological Roles
![Page 36: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/36.jpg)
c-Abl Kinase Domain Structure
![Page 37: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/37.jpg)
STI-571
![Page 38: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/38.jpg)
STI-571
![Page 39: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/39.jpg)
STI-571
www.cmlsupport.com
![Page 40: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/40.jpg)
![Page 41: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/41.jpg)
![Page 42: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/42.jpg)
![Page 43: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/43.jpg)
![Page 44: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/44.jpg)
![Page 45: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/45.jpg)
![Page 46: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/46.jpg)
![Page 47: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/47.jpg)
![Page 48: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/48.jpg)
Parametric Linkage analysis
![Page 49: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/49.jpg)
![Page 50: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/50.jpg)
![Page 51: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/51.jpg)
![Page 52: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/52.jpg)
3
![Page 53: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/53.jpg)
![Page 54: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/54.jpg)
![Page 55: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/55.jpg)
![Page 56: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/56.jpg)
![Page 57: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/57.jpg)
Fig. 1. The β-catenin protein interaction network.
Michael B. Major et al. Science 2007;316:1043-1046
Published by AAAS
![Page 58: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/58.jpg)
Fig. 3. WTX promotes β-catenin ubiquitination and degradation.
Michael B. Major et al. Science 2007;316:1043-1046
Published by AAAS
![Page 59: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/59.jpg)
![Page 60: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/60.jpg)
![Page 61: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/61.jpg)
![Page 62: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/62.jpg)
Tumour Suppressors
•Example 4: REST
![Page 63: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/63.jpg)
![Page 64: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/64.jpg)
![Page 65: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/65.jpg)
![Page 66: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/66.jpg)
![Page 67: Finding Cancer Genes](https://reader036.vdocuments.net/reader036/viewer/2022062719/56649ef15503460f94c02b30/html5/thumbnails/67.jpg)
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