Genetics 144, Oncogenomics

Darmouth Medical School

Spring 2008, Mondays, 1:15-4

Charles Brenner, Ph.D.

charles.brenner@dartmouth.edu

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From the Dartmouth ORC:
Cancer is not one disease but hundreds of different diseases caused by hundreds of different genotypes. At the cusp of the era in which it has become possible to classify tumors molecularly and to develop targeted therapeutics, this course will explore the impact of genomics on cancer prevention, detection, classification and treatment. Working with a new textbook and the primary literature, students will present research projects on molecular profiling, model systems, and molecularly targeted drugs and imaging.

The course is based on the new book, Oncogenomics: Molecular Approaches to Cancer, edited by Charles Brenner and David Duggan. The book (March 2004, 382 pages, ISBN 0-471-22592-4) is available from Wiley and Amazon. Please read Dr. Franco Cavalli's review of Oncogenomics in the New England Journal of Medicine.

 


Detailed syllabus

Week 1. At the Precarious Cusp of Oncogenomics
3/24/08, Rubin, Aud G
(Read Chapter 1 in advance)
Review of Basic Cancer Genetics.
Introduction to Expression-Profiling.
Introduction to Model Systems.
Introduction to Molecularly Targeted Drugs and Testing.
Nontechnological Roadblocks to Oncogenomic Advances.
Course requirements and discussion questions for Week 1.

Week 2. Genome-wide Searches for Mutations in Human Cancers
3/31/08, Rubin 852
(Read Chapter 2 and presentation papers in advance)
Homozygous deletions.
Small intragenic mutations.
Chromosomal rearrangements.
Copy changes.
Methylation status changes.
2005 report presentations: Rob Lampman on Paez and Paula Knittle on Lynch.
2006 report presentation: Seth Ziegler on Davies.
2008 report presentation: Seth Brown on Sjoblom and Wood.
Discussion questions for Week 2.

Week 3. Array-based Comparative Genomic Hybridization and SNPs
4/7/08, Rubin Aud G
(Read Chapters 3, 4 and presentation papers in advance)
Cancer Gene Discovery by CGH.
Targeted CGH.
Disease Classification by CGH.
Haplotype Association of SNPs by Linkage Disequilibrium.
Confirming Association of SNPs and Disease.
2005 report presentations: Eyal Amiel on Barrett and Tagawa; Scott Gleim on Kammerer and Gold.
2006 report presentation: Athena Nomikos on Ellis.
2008 report presentation: Peter Belenky on Weir.
Discussion questions for Week 3.

Week 4. RNA Expression Profiling in Cancer
4/14/08, Rubin 852
(Read Chapters 5, 6 and presentation papers in advance)
Gene Clustering in Microarrays.
Disease Classification.
Gene Discovery by Microarray.
Phenocopies of Disease Mutations.
Combined Linkage and Microarray Analysis.
2005 report presentations: Justin Gaudet on Ma & Ma and Huan Liu on Lamb.
2006 report presentation: Seung Hyuk Choi on Bild.
2008 report presentation: Jessie Blackburn on Wong.
Discussion questions for Week 4.

Week 5. The NCI-60 and Tissue Analysis in Cancer
4/21/08, Rubin 852
(Read Chapters 7, 8 and presentation papers in advance)
Pharmacological Profiling of cancer-derived cell lines.
Expression Profiling of the NCI-60.
Correlations of genes and drugs.
Laser capture microdissection of tumor tissue.
Layered expression scanning and tissue microarrays.
2005 report presentations: Michael Gleeson on Jacquemier, Kristen Garner on Szakacs, and Mark Yore on Dolma.
2006 report presentations: Maximillian Rogers on Pages and Justine Hutchinson on Garraway.
2008 report presentation: Swapna Kollu on Qiu and Sierra Kent on Lee.
Discussion questions for Week 5.

Week 6. Proteomics and Model Systems in Cancer
4/28/08, Rubin 852
(Read Chapters 9, 10 and presentation papers in advance)
Gel, mass-spec and hybridization-based methods for protein profiling.
Chemical genetics.
Yeast, fly and zebrafish approaches to discover and validate drugs targets.
2005 report presentations: Summer Gibbs on Young and Gudrun Bjornsdottir on Berghmans.
2006 report presentation: Youngsoo Jun on Lackner.
2008 report presentations: Dustin Elwood on Kang and Matthew Wood on Langenau.
Discussion questions for Week 6.

Week 7. Mouse Models of Cancer
5/5/08, Rubin 852
(Read Chapters 11, 12 and presentation papers in advance)
Oncogene models.
Tumor suppressor models.
Analysis of mouse models.
Quantitative Trait Locus Analysis of Colon Cancer Incidence in Mouse.
Forward and Reverse Modifier Screens for Penetrance Effects.
2005 report presentations: Michael Chen on Mao and Shinichiro Fuse on Olive.
2006 report presentation: Anna Wasiuk on Nateri.
2008 report presentations: Mandeep Kaur on Li and Li-ju Chang on Reinhardt.
Discussion questions for Week 7.

Week 8. Molecularly Targeted Drugs
5/12/08, Rubin 852
(Read Chapters 13, 14 and presentation papers in advance)
Kinases as Targets.
GTPases as Targets.
2005 report presentations: Shohreh Farzan on O'Hare and Zhiyong Gao on Onda.
2006 report presentations: Patrick Cushing on Solit and Samuel Bakhoum on Farmer.
2008 report presentations: Paul Huang on Rhodes and Haoxu Ouyang on Caunt.
Discussion questions for Week 8.

Week 9. Targeted Testing and the Future of Oncogenomics
5/19/08, Rubin 852
(Read Chapters 15, 16 and presentation papers in advance)
Economic and Ethical Challenges of Targeted Testing.
The NCI Director's Challenge.
2005 report presentations: Bethany Merenick on O'Farrell and Micah Benson on Debiec-Rychter.
2006 report presentation: Erika Artinger on Shepherd and Tsao.
2008 report presentations: Nadia Penrod on deHaas and Aimee Pike on Moore and Frolov.
Discussion questions for Week 9.


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