Fall 2008

Biology 165A
Molecular Genetics of Cancer

Schedule

Please note that this schedule is tentative and still subject to change

Date Topic Weinberg Articles Presenter Assignment
Sept  3 Introduction to course Profs. Seligman and Hamlett
 
Sept  8 Introduction to cancer 2.1
2.4–2.11
11.1–11.5
Prof. Seligman
PowerPoint
Sept 10 Viruses & cancer — an introduction 3.1–3.3
3.5–3.12
Rous, P. 1911. Transmission of a malignant new growth by means of a cell-free filtrate. JAMA 56: 471. [pdf]

Martin, G. S. 1970. Rous sarcoma virus: A function required for the maintenance of the transformed state. Nature 227: 1021-1023. [pdf]

Stehelin, D., H.E. Varmus, J.M. Bishop, and P.K. Vogt. 1976. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 260: 170-173. [pdf]

Martin, G.S. 2001. The hunting of the Src. Nat Rev Mol Cell Biol 2: 467-475 [html | pdf]
Prof. Hamlett
PowerPoint
3 questions for Weinberg

No assignment for articles
 
Sept 15 Oncogenes 4.2–4.3 Shih, C., and R.A. Weinberg. 1982. Isolation of a transforming sequence from a human bladder carcinoma cell line. Cell 29: 161-169. [pdf] Sam Cook
PowerPoint
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3 questions for Weinberg

Questions for article
Sept 17 Oncogenes (cont) 4.4–4.6 Tabin, C.J., S.M. Bradley, C.I. Bargmann, R.A. Weinberg, A.G. Papageorge, E.M. Scolnick, R. Dhar, D.R. Lowy, and E.H. Chang. 1982. Mechanism of activation of a human oncogene. Nature 300: 143-149. [pdf] Ray Addante
PowerPoint
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3 questions for Weinberg

Summary for article
 
Sept 22 Oncogenic pathways 5.1–5.5
5.9, 6.1
Collett, M.S. and R.L. Erikson. 1978. Protein kinase activity associated with the Avian Sarcoma Virus src gene product. PNAS 75: 2021-2024. [pdf]

Bryant, D., and J.T. Parsons. 1983. Site-directed point mutation in the src gene of Rous Sarcoma Virus result in an inactive src gene product. J. Virol. 45: 1211-1216. [pdf | Fig2 | Fig3 | Fig4]

Smith, M.R., S.J. DeGudicibus, and D.W. Stacey. 1986. Requirement of c-ras proteins during viral oncogene transformation. Nature 320: 540-543. [pdf]
Group presentations & class discussion 3 questions for Weinberg

Group Presentation Instructions
Sept 24 Introduction to tumor suppressors 7.1–7.6 Leppert, M., M. Dobbs, P. Scambler, P. O’Connell, Y. Nakamura, D. Stauffer, S. Woodward, R. Burt, J. Hughes, E. Gardner, M. Lathrop, J. Wasmuth, J.-M. Lalouel, and R. White. 1987. The gene for familial polyposis coli maps to the long arm of chromosome 5. Science 238: 1411-1413. [html | pdf]

Fearon, E. R., K. R. Cho, J. M. Nigro, S. E. Kern, J. W. Simons, J. M. Ruppert, S. R. Hamilton, A. C. Preisinger, G. Thomas, K. W. Kinzler, B. Vogelstein. 1990. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 247: 49-56. [html | pdf]
Prof. Seligman
PowerPoint
3 questions for Weinberg

No assignment for articles
 
Sept 29 Tumor suppressor genes 7.7–7.13 Knudson, A. G. 1971. Mutation and cancer: A statistical study of retinoblastoma. PNAS 68: 820-823. [pdf] Andrea Cohen
PowerPoint
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3 questions for Weinberg

Questions for article
Oct  1 More Tumor suppressor genes Cavenee, W.K., T.P. Dryja, R.A. Phillips, W.F. Benedict, R.Godbout, B.L. Gallies, A.L. Murphree, L.C. Strong, and R.L. White. 1983. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 305: 779-784. [pdf | Clearer gel photos are available on Sakai] Kendra Henderson
PowerPoint
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Read Cavenee et al. (1983)

Write a News Release for Lee et al. (1987)
Lee, W.-H., R. Bookstein, F, Hong, L.-J. Young, J.-Y. Shew, and E.Y.-H. P. Lee. 1987. Human retinoblastoma susceptibility gene: Cloning, identification, and sequence. Science 235: 1394-1399. [html | pdf] Allison Dubner
PowerPoint
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Oct  6 Introduction to cell cycle 8.1–8.4
8.12
Hartwell, L. H. 1991. Twenty-five years of cell cycle genetics. Genetics 129: 975-980. [pdf]

Hartwell, L. H., J. Culotti, J. R. Pringel, and B. J. Reid. 1974. Genetic control of the cell division cycle in yeast. Science 183: 46-51. [html | pdf]

Lee, M. G., and P. Nurse. 1987. Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature 327: 31-35. [pdf]
Prof. Seligman
PowerPoint
3 questions for Weinberg

No assignment for articles
Oct  8 Cell cycle 8.6–8.8 Nurse, P., and P. Thuriaux. 1980. Regulatory genes controlling mitosis in the fission yeast Schizosaccharomyces pombe. Genetics 96: 627-637. [pdf] Doug Campbell
PowerPoint
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3 questions for Weinberg

Summary for article
 
Oct 13 Checkpoints 8.9-8.13 Weinert, T. A., and L. H. Hartwell. 1988 The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae. Science 241: 317-322. [html | pdf] Doug Farquhar
PowerPoint
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3 questions for Weinberg

Summary for article
Oct 15

MIDTERM EXAM

 
Oct 20

FALL BREAK - no class

Oct 22 Checkpoints (cont) 12.11-12.12 Cahill, D. P., C. Lengauer, Yu, G. J. Riggins, J. K. V. Willson, S. D. Markowitz, K. W. Kinzler, and B. Vogelstein. 1998. Mutations of mitotic checkpoint genes in human cancers. Nature 392: 300-303 [html | pdf] Michael Klein
PowerPoint
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3 questions for Weinberg

Summary for article
 
Oct 27 DNA tumor viruses & p53 3.4
9.1–9.4
Levine, A. J., C. A. Finlay, and P. W. Hinds. 2004. P53 is a tumor suppressor gene. Cell 116: S67-S69. (Commentary) [pdf]

Crawford, L. V., D. C. Pim, E. G. Gurney, P. Goodfellow, and J. Taylor-Papadimitriou. 1981. Detection of a common feature in several human tumor cell lines—A 53,000-Dalton Protein. Proc. Nat. Acad. Sci. USA 78[Part 2: Biological Sciences]: 41-45. [pdf | High-resolution figures in JSTOR: Fig1 | Fig2 | Fig3 | Fig4 | Fig5 | Fig6]

Finlay, C. A., P. W. Hinds, and A. J. Levine. 1989. The p53 proto-oncogene can act as a suppressor of transformation. Cell 57: 1083-1093. [pdf]
Prof. Hamlett 3 questions for Weinberg

No assignment for articles
Oct 29 p53 9.5–9.7 Baker, S. J., S. Markowitz, E. R. Fearon, J. K. V. Willson, and B. Vogelstein. 1990. Suppression of human colorectal carcinoma cell growth by wild-type p53. Science 249: 912-915. [html | pdf] Andrea Cohen
PowerPoint
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3 questions for Weinberg

Write a News Release for Donehower et al. (1992)
Donehower, L. A., J. Harvey, B. L. Slagle, M. J. McArthur, C. A. Montgomery, Jr., J. S. Butel, and A. Bradley. 1992. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumors. Nature 356: 215-221. [pdf | Some gels are clearer in these figures on Sakai] Doug Campbell
PowerPoint
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Nov  3 p53 (cont) 9.8–9.10
9.13–9.14
Lowe, S. W., E. M. Schmitt, S. W. Smith, B. A. Osborne, and T. Jacks. 1993. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362: 847-849. [pdf] Doug Farquhar
PowerPoint Feedback
3 questions for Weinberg

Questions for the two articles
Polyak, K., Y. Xia, J. L. Zweier, K. W. Kinzler, and B. Vogelstein. 1997. A model for p53-induced apoptosis. Nature 389: 300-305. [html | pdf | Fig1 | Fig2 | Fig3 | Fig4] Sam Cook
PowerPoint Feedback
Nov  5 p53 (cont) 9.11–9.12 Venkatachalam S., Y. P. Shi, S. N. Jones, H. Vogel, A. Bradley, D. Pinkel, and L. A. Donehower. 1998. Retention of wild-type p53 in tumors from p53 heterozygous mice: Reduction of p53 dosage can promote cancer formation. EMBO J. 17: 4657-4667. [html | pdf]

Lang, G., T. Iwakuma, Y. Suh, G. Liu, V. Rao, J. Parant, Y. Valentin-Vega, T. Terzian, L. Caldwell, and L. Strong. 2004. Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni Syndrome. Cell 119: 861-872. [html | pdf]
Class discussion No questions for Weinberg

Discussion assignment
 
Nov  10 Introduction to telomeres and telomerase 10.1–10.2
10.4–10.6
Greider, C. W., and E. H. Blackburn. 1985. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43: 405-413. [html | pdf]

Yu, G., J. D. Bradley, L. D. Attardi, and E. H. Blackburn. 1990. In vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs. Nature 344: 126-131. [pdf]

Shay, J. W., and W. E. Wright. 2000. TIMELINE: Hayflick, his limit, and cellular ageing. Nat. Rev. Mol. Cell Biol. 1: 72-76. [html | pdf]

Kim, N. W., M. A. Piatyszek, K. R. Prowse, C. B. Harley, M. D. West, P. L. C. Ho, G. M. Coviello, W. E. Wright, S. L. Weinrich, and J. W. Shay. Specific association of human telomerase activity with immortal cells and cancer. Science 266: 2011-2015. [JSTOR: html | pdf]
Prof. Hamlett 3 questions for Weinberg

No assignment for articles
Nov 12 Immortality 10.7-10.11 Blasco, M.A., H-W. Lee, M.P. Hande, E. Samper, P.M. Lansdorp, R.A. DePinho, and C.W. Greider. 1997. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91: 25-34. [html | pdf] Michael Klein
PowerPoint
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3 questions for Weinberg

Summaries for each of the two articles
Artandi, S. E., S. Chang, S.L. Lee, S. Alson, G. J. Gottlieb, L. Chin, and R. A. DePinho. 2000. Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature 406: 641-645. [html | pdf | Fig1 | Fig2 | Fig3] Raymond Addante
PowerPoint
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Nov 17 Multi-step carcinogenesis 11.9-11.11 Hahn, W. C., C. M. Counter, A. S. Lundberg, R. L. Beijersbergen, M. W. Brook, and R. A. Weinberg. 1999. Creation of human tumour cells with defined genetic elements. Nature 400: 464-468. [html | pdf | Fig1 | Fig2 | Fig3 | Fig4] Jordan Eboreime
PowerPoint
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3 questions for Weinberg
Summary for article
Introduction to mutators 12.3-12.8 Hoess, R. H., and R. K.,Herman. 1975. Isolation and characterization of mutator strains of Escherichia coli K-12.J. Bacteriol. 122(2): 474-484. [pdf]

Nghiem, Y., M. Cabrera, C. G. Cupples, and J. H. Miller. 1988. The mutY gene: A mutator locus in Escherichia coli that generates GC to TA transversions. PNAS 85: 2709-2713. [pdf]

Michaels, M.L., C. Cruz, A. P. Grollman, and J. H. Miller. 1992. Evidence that MutY and MutM combine to prevent mutations by an oxidatively damaged form of guanine in DNA. PNAS 89: 7022-7025. [pdf]

Reenan, R. A., and R. D. Kolodner. 1992. Isolation and characterization of two Saccharomyces cerevisiae genes encoding homologs of the bacterial HexA and MutS mismatch repair proteins. Genetics 132: 963-973. [pdf]

Strand, M., T. A. Prolla, R. M. Liskay, and T. D. Petes. 1993. Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature 365: 274-276. [pdf]
Prof. Seligman
PowerPoint
3 questions for Weinberg

No assignment for articles
Nov 19 Genomic integrity 12.9-12.10 Fishel, R., M. K. Lescoe, M. R. S. Rao, N. G. Copeland, N. A. Jenkins, J. Garber, M. Kane, and R. Kolodner. 1993. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75: 1027-1038. [pdf] Allison Dubner
PowerPoint
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3 questions for Weinberg

Summary for article
 
Nov 24 Mutators and cancer Nicolaides, N. C., S. J. Littman, P. Modrich, K. W. Kinzler, and B. Vogelstein. 1998. A naturally occurring hPMS2 mutation can confer a dominant negative mutator phenotype. Mol. Cell. Biol. 18: 1635-1641. [html | pdf | Fig1 | Fig2 | Fig3 | Fig4 | Fig5 | Fig6] Kendra Henderson
PowerPoint
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Summary for article
Nov 26

Pre-Thanksgiving Break - no class

 
Dec  1 Stem cells and cancer 11.6., 12.2 Al-Hajj, M. S. Wicha, A. Benito-Hernandez, S. J. Morrison, and M. F. Clarke. 2003. Prospective identification of tumorigenic breast cancer cells. PNAS 100(7): 3983-3988. [html | pdf] Jordan Eboreime
PowerPoint
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3 questions for Weinberg

Summary for article
Dec  3 Optional consultations on Final Projects  
 
Dec  8 Final project presentations Raymond Addante
Andrea Cohen
Doug Farquhar
Dec  10 Final project presentations Michael Klein
Doug Campbell
Jordan Eboreime
Dec  16
2 pm
Final project presentations Allison Dubner
Kendra Henderson
Sam Coook

Page last updated 2 December 2008 by Nancy Hamlett.