CANB 610:Materials

• • IN PROGRESS**

Class Focus, Winter 2012

1. Organization Meeting and Rules of Engagement
2. Genomics and Cancer
3. Genomic instability and Cancer
4. Drug Discovery

Organizational Meeting: Introduction and Scheduling

Presentation Zen

1. Slide Zen
2. Delivery Zen
3. Feel free to add links that help you

Evaluation Forms

• Evaluation Form MC
• Evaluation Form Presenter 1(Intro)
• Evaluation Form Presenter 2
• Dept. Evaluation Form

Week 1: Tumor Sequencing, part 1

Papers

1. Guo G, Gui Y, Gao S, Tang A, Hu X, Huang Y, Jia W, Li Z, He M, Sun L, Song P, Sun X, Zhao X, Yang S, Liang C, Wan S, Zhou F, Chen C, Zhu J, Li X, Jian M, Zhou L, Ye R, Huang P, Chen J, Jiang T, Liu X, Wang Y, Zou J, Jiang Z, Wu R, Wu S, Fan F, Zhang Z, Liu L, Yang R, Liu X, Wu H, Yin W, Zhao X, Liu Y, Peng H, Jiang B, Feng Q, Li C, Xie J, Lu J, Kristiansen K, Li Y, Zhang X, Li S, Wang J, Yang H, Cai Z, and Wang J. Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma. Nat Genet. 2011 Dec 4;44(1):17-9. DOI:10.1038/ng.1014 |

Bonus Materials

• Kidney cancer http://www.ncbi.nlm.nih.gov/pubmed/20368728
• Mutations in cancer http://www.ncbi.nlm.nih.gov/pubmed/17932254
• Hallmarks of cancer http://www.ncbi.nlm.nih.gov/pubmed/21376230
• Sequencing technologies http://www.ncbi.nlm.nih.gov/pubmed/20847746

and then a bit of a leap:

• Application to clinic http://www.ncbi.nlm.nih.gov/pubmed/22133722

Lecture Slides

• ion torrent video
• File:Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway.pptx
• Lectures on genomics 13 week Series on Genomics 2012 on YouTube
• Spectra of Somatic Mutations Michael Lawrence lecture from 2011 TCGA conference on somatic mutation heterogeneity

Week 2: Tumor Sequencing, part 2

Papers

2. Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, Cook K, Stepansky A, Levy D, Esposito D, Muthuswamy L, Krasnitz A, McCombie WR, Hicks J, and Wigler M. Tumour evolution inferred by single-cell sequencing. Nature. 2011 Apr 7;472(7341):90-4. DOI:10.1038/nature09807 |

Bonus Materials

• Previous work from Wigler on progression http://www.ncbi.nlm.nih.gov/pubmed/19903760
• Old work on heterogeneity http://www.ncbi.nlm.nih.gov/pubmed/9108466
• Evolution by serial sampling http://www.ncbi.nlm.nih.gov/pubmed/20393555
• Evolution in pancreatic cancer http://www.ncbi.nlm.nih.gov/pubmed/20981101
• Mathematical treatment of rearrangement phylogeny (suggested by Paul) http://www.ncbi.nlm.nih.gov/pubmed/21994251
• Michor (suggested by Paul) http://www.ncbi.nlm.nih.gov/pubmed/20864632

• Taniguchi paper on BRCA2 compensatory mutations following cisplatin http://www.ncbi.nlm.nih.gov/pubmed/18264087
• Ashworth paper on BRCA2 compensatory mutations in Ovarian cancer following PARPi http://www.ncbi.nlm.nih.gov/pubmed/18264088

Week 3: RNA sequencing

Papers

3. Li M, Wang IX, Li Y, Bruzel A, Richards AL, Toung JM, and Cheung VG. Widespread RNA and DNA sequence differences in the human transcriptome. Science. 2011 Jul 1;333(6038):53-8. DOI:10.1126/science.1207018 |
4. Paz N, Levanon EY, Amariglio N, Heimberger AB, Ram Z, Constantini S, Barbash ZS, Adamsky K, Safran M, Hirschberg A, Krupsky M, Ben-Dov I, Cazacu S, Mikkelsen T, Brodie C, Eisenberg E, and Rechavi G. Altered adenosine-to-inosine RNA editing in human cancer. Genome Res. 2007 Nov;17(11):1586-95. DOI:10.1101/gr.6493107 |
5. Langmead B, Trapnell C, Pop M, and Salzberg SL. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009;10(3):R25. DOI:10.1186/gb-2009-10-3-r25 |
6. Trapnell C, Pachter L, and Salzberg SL. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics. 2009 May 1;25(9):1105-11. DOI:10.1093/bioinformatics/btp120 |
7. Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, Salzberg SL, Wold BJ, and Pachter L. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 2010 May;28(5):511-5. DOI:10.1038/nbt.1621 |

Bonus Materials

8. Very Few RNA and DNA Sequence Differences in the Human Transcriptome http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0025842

9. Post on Paralogs and Splice Junctions http://www.genomesunzipped.org/2011/05/notes-on-the-evidence-for-extensive-rna-editing-in-humans.php

10. nice pictures for presentations http://www.sciencephoto.com/search?subtype=keywords&searchstring=transcription&oldsearchstring=ribosome&matchtype=&sort_results=&media_type=images&license=all&channel=all&Search.x=0&Search.y=0

Lecture Slides

• Widespread RNA and DNA differences

Week 4: Functional Genomics

Papers

11. Possemato R, Marks KM, Shaul YD, Pacold ME, Kim D, Birsoy K, Sethumadhavan S, Woo HK, Jang HG, Jha AK, Chen WW, Barrett FG, Stransky N, Tsun ZY, Cowley GS, Barretina J, Kalaany NY, Hsu PP, Ottina K, Chan AM, Yuan B, Garraway LA, Root DE, Mino-Kenudson M, Brachtel EF, Driggers EM, and Sabatini DM. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature. 2011 Aug 18;476(7360):346-50. DOI:10.1038/nature10350 |
12. Premsrirut PK, Dow LE, Kim SY, Camiolo M, Malone CD, Miething C, Scuoppo C, Zuber J, Dickins RA, Kogan SC, Shroyer KR, Sordella R, Hannon GJ, and Lowe SW. A rapid and scalable system for studying gene function in mice using conditional RNA interference. Cell. 2011 Apr 1;145(1):145-58. DOI:10.1016/j.cell.2011.03.012 |

http://www.nature.com/nrc/journal/v11/n9/full/nrc3128.html Jones, R. G. & Thompson, C. B. Tumor suppressors and cell metabolism: a recipe for cancer growth.Genes Dev. 23, 537–548 (2009)

Lecture slides

Introduction: Cancer Metabolism, Functional Genomics, and Breast Cancer
Results: Functional Genomics Reveal that the Serine Synthesis Pathway is Essential in Breast Cancer

General Background for Genomic Instability and Cancer

• The DNA damage response and cancer therapy http://www.ncbi.nlm.nih.gov/pubmed/22258607
• Defining 'chromosomal instability'. http://www.ncbi.nlm.nih.gov/pubmed/18192061

Week 6: Chromothripsis

Papers

13. Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, Morsberger LA, Iacobuzio-Donahue C, Follows GA, Green AR, Flanagan AM, Stratton MR, Futreal PA, and Campbell PJ. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell. 2011 Jan 7;144(1):27-40. DOI:10.1016/j.cell.2010.11.055 |

Bonus Materials

link to Cell podcast by the author

Week 7: Circadian rhythm and cancer

Papers

• Control of skin cancer by the circadian rhythm http://www.ncbi.nlm.nih.gov/pubmed/22025708

Bonus Materials

• Does evening sun increase the risk of skin cancer? http://www.ncbi.nlm.nih.gov/pubmed/22084098
• Circadian clock control of the cellular response to DNA damage http://www.ncbi.nlm.nih.gov/pubmed/20227409
• Circadian rhythms and tumor growth http://www.ncbi.nlm.nih.gov/pubmed/22252116
• Circadian Integration of Metabolism and Energetics http://www.ncbi.nlm.nih.gov/pubmed/21127246
• The genetics of mammalian circadian order and disorder: implications for physiology and disease http://www.ncbi.nlm.nih.gov/pubmed/18802415
  
• Circadian timing in cancer treatment http://www.ncbi.nlm.nih.gov/pubmed/20055686

Presentations

• Introduction:Control of skin cancer by the circadian rhythm
• Results: Control of skin cancer by the circadian rhythm

Week 8: Inflammation and cancer

Papers

• The Mutyh Base Excision Repair Gene Influences the Inflammatory Response in a Mouse Model of Ulcerative Colitis http://www.ncbi.nlm.nih.gov/pubmed/20706593
• DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. http://www.ncbi.nlm.nih.gov/pubmed/18521188

Bonus Materials

• Base Excision Repair and Lesion-Dependent Subpathways for Repair of Oxidative DNA Damage http://www.ncbi.nlm.nih.gov/pubmed/20649466
• Intestinal Inflammation and Cancer http://www.ncbi.nlm.nih.gov/pubmed/21530747

Lecture Slides

• Background: Inflammation and Cancer

Week 9: Drug Development part 1 GIST

Papers

• ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumours http://www.nature.com/nature/journal/v467/n7317/full/nature09409.html

Bonus Materials

See supplemental materials including excel spreadsheets and movies that accompany the main paper

• Cancer: Oncogenes in context. http://www.nature.com/nature/journal/v467/n7317/full/467796a.html

Lecture Slides

• Introduction: GI Stromal Tumors and ETV1
• Results: GIST and ETV1

Week 11: Drug Development part 2

Papers

• The secret ally: immunostimulation by anticancer drugs. http://www.ncbi.nlm.nih.gov/pubmed/22301798