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Genomic sequencing for the Cancer Genome Atlas and clinical translation

Genomic sequencing for the Cancer Genome Atlas and clinical translation. Chris Sander Computational & Systems Biology MSKCC Memorial Sloan-Kettering Cancer Center New York. New York Biotechnology Association NYBA 2-May-2012 @ NYC. The Cancer Genome Atlas Research Network.

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Genomic sequencing for the Cancer Genome Atlas and clinical translation

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  1. Genomic sequencing for the Cancer Genome Atlas and clinical translation Chris Sander Computational & Systems Biology MSKCCMemorial Sloan-Kettering Cancer Center New York New York Biotechnology Association NYBA 2-May-2012 @ NYC

  2. The Cancer Genome Atlas Research Network

  3. A global project Australia Canada China France Germany India Italy Japan Spain UK US >20M € 1-2 cancer types / country

  4. TCGA: Massive Sequencing and more • Multiple data types • Clinical diagnosis • Treatment history • Histologic diagnosis • Pathologic report/images • Tissue anatomic site • Surgical history • Gene expression/RNA sequence • Chromosomal copy number • Loss of heterozygosity • Methylation patterns • miRNA expression • DNA sequence • RPPA (protein) • Subset for Mass Spec 25 forms of cancer glioblastoma multiforme(brain) squamous carcinoma(lung) serouscystadenocarcinoma(ovarian) Etc. Etc. Etc. Biospecimen CoreResource with more than 150 Tissue Source Sites 6 Cancer GenomicCharacterization Centers 3 GenomeSequencingCenters 7 Genome Data Analysis Centers Data Coordinating Center

  5. Whole genome sequencing in cancer 7 Prostate 5 Melanoma 7/9 Colon 5 Ovarian WGS Whole genome sequencing 5 Brain Mike Lawrence, Broad Inst TCGA & other data 2011-10-6 3 CLL … 23 MM

  6. Diversity of DNA segment alterations across cancer types brain ovarian * hypermutated colorectal lung breast TCGA data / IGV / Niki Schultz

  7. Ovarian cancer: DNA repair weakened 47% of patients affected by alterations in this gene set The Cancer Genome Atlas Network – TCGA The Cancer Genome Atlas Network – TCGA – Nature, 2011 N.Schultz, E.Cerami, D.Levine, P. Spellman et al.

  8. Ovarian cancer: DNA repair weakened Drug trials for these patients using PARP inhibitors? The Cancer Genome Atlas Network – TCGA – Nature, 2011 N.Schultz, E.Cerami, D.Levine, P. Spellman et al.

  9. Prostate cancer: DNA segment alterations

  10. Prostate cancer: much better prognosis for patients with fewer DNA segment alterations

  11. Prostate cancer: much better prognosis for patients with fewer DNA segment alterations

  12. Prostate cancer: much better prognosis for patients with fewer DNA segment alterations less aggressive treatment?

  13. www.cbioportal.org • Cancer Genomics PortalDecision Support System for Clinical Research cBio@MSKCC, Cancer Discovery, in press

  14. Contributions based on massive DNA sequencing Future 1: New drug targets Future 2: Precision Medicine

  15. Massive genomic sequencing reveals protein evolution RAS protein family: and oncogene and its relatives

  16. 3D protein structures from next-gen sequencing Evolutionary information & statistics & physics www.EVfold.org

  17. 3D protein structures from next-gen sequencing Test: RAS cancer protein observed www.EVfold.org

  18. 3D protein structures from next-gen sequencing Test: RAS cancer protein EVfold predicted observed www.EVfold.org

  19. 3D protein structures from next-gen sequencing Test: RAS cancer protein observed predicted compared www.EVfold.org

  20. New drug targets predicted in 3D www.EVfold.org Sander Group / MSKCC, Marks Group / HMS - Cell, 10 May 2012

  21. Future 2: Precision Medicine Clever & massively parallel DNA and RNA sequencing in a clinical setting: • New therapeutic targets • Prognosis • Biomarkers of response • Choice of therapy

  22. Future 2: Precision Medicine Clever & massively parallel DNA and RNA sequencing in a clinical setting: • New therapeutic targets • Prognosis • Biomarkers of response • Choice of therapy Targeted therapies tailored to the individual.

  23. Future 2: Precision Medicine Clever & massively parallel DNA and RNA sequencing in a clinical setting: • New therapeutic targets • Prognosis • Biomarkers of response • Choice of therapy Targeted therapies tailored to the individual.

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