Introduction cancer genetics and genomics

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Introduction cancer genetics and genomics

  1. 1. Introduction to cancergenetics and genomics Nuria Lopez-Bigas• Molecular bases of cancer• Cancer alterations and technologies to detect them genome-wide• Predictive cancer genomics• NGS technologies in cancer research
  2. 2. Mutations: Somatic and GermlineSomatic mutations Germline mutations Occur in nongermline tissues Present in egg or sperm Are nonheritable Are heritable Cause cancer family syndrome NonheritableSomatic mutation Mutation in All cells (e.g., breast) egg or sperm affected in offspring
  3. 3. Hallmarks of Cancer Hanahan & Weinberg. Cell. 2000 Jan 7;100(1):57-70
  4. 4. Hallmarks of Cancer Hanahan & Weinberg. Cell. 2000 Jan 7;100(1):57-70
  5. 5. Genomic and epigenomic aberrations in cancer
  6. 6. High-throughput technologies to identify cancer alterations
  7. 7. Expression microarrays
  8. 8. Comparative Genomics Hybridization (CGH)
  9. 9. Comparative Genomics Hybridization (CGH)
  10. 10. DNA Sequencing Science 13 October 2006
  11. 11. Sjoblom et al., Science 2006
  12. 12. Detecting the Troublemakers
  13. 13. Drivers vs Passengers Straton et al., Nature. 2009 Apr 9;458(7239):719-24.
  14. 14. Cancer genome characterization Chin and Gray. Nature 452, 553-563(3 April 2008)
  15. 15. Chin and Gray. Nature 452, 553-563(3 April 2008)
  16. 16. Various alterations affecting the same pathway Chin and Gray. Nature 452, 553-563(3 April 2008)
  17. 17. Molecular Diagnostics of Cancer Laura J. van t Veer & René Bernards. Nature 452, 564-570(3 April 2008)
  18. 18. Generating a prognostic gene- expression signature Laura J. van t Veer & René Bernards. Nature 452, 564-570(3 April 2008)
  19. 19. 70 gene prognostic signature in breast cancer Text Laura J. van t Veer, et al. Nature 415, 530-536(31 January 2002)
  20. 20. 70 gene prognostic signature in breast cancer Text Laura J. van t Veer, et al. Nature 415, 530-536(31 January 2002)
  21. 21. Oncotype DX: 21 gene signature in breast cancer for predicting distance recurrence My RS is 30. What is the chance of recurrence within 10 years? 95% CI
  22. 22. Oncotype DX: 21 gene signature in breast cancer for predicting distance recurrenceDistant Recurrence for the three distinct cohorts identified 100% 90% Proportion without Distant Recurrence 80% 70% 60% 50% P <0.001 40% 30% RS <18 n = 338 20% RS 18-30 n = 149 10% RS !31 n = 181 0% 0 2 4 6 8 10 12 14 16 Years Paik et al. N Engl J Med. 2004;351:2817-2826.
  23. 23. Oncotype DX: 21 gene signature in breast cancer for predicting distance recurrence Recurrence Score in N-, ER+ patients1) Paik et al NEJM 2004, 2) Habel et al Breast Cancer Research 20063) Paik et al JCO 2006, 4) Gianni et al JCO 2005
  24. 24. Next Generation Sequencing Revolution Straton et al., Nature. 2009 Apr 9;458(7239):719-24.
  25. 25. Template preparationSequencingImagingData processing
  26. 26. Template preparation Clonally amplified templates from a single DNA molecule Emulsion PCR Solid Phase Amplification Single DNA molecule Primer immobilized Template immobilized Polymerase immobilized
  27. 27. Template preparation Clonally amplified templates from a single DNA molecule Emulsion PCR Solid Phase Amplification Michael L. Metzker. Nature Reviews Genetics 11, 31-46 (January 2010)
  28. 28. Template preparation Clonally amplified templates from a single DNA molecule Emulsion PCR Solid Phase Amplification Michael L. Metzker. Nature Reviews Genetics 11, 31-46 (January 2010)
  29. 29. Template preparation Clonally amplified templates from a single DNA molecule Emulsion PCR Solid Phase Amplification Single DNA molecule Primer immobilized Template immobilized Polymerase immobilized Michael L. Metzker. Nature Reviews Genetics 11, 31-46 (January 2010)
  30. 30. Template preparation Clonally amplified templates from a single DNA molecule Emulsion PCR Solid Phase Amplification Single DNA molecule Primer immobilized Template immobilized Polymerase immobilized Michael L. Metzker. Nature Reviews Genetics 11, 31-46 (January 2010)
  31. 31. Sequencing/ImagingMichael L. Metzker. Nature Reviews Genetics 11, 31-46 (January 2010)
  32. 32. Sequencing/Imaging
  33. 33. Sequencing/ImagingMichael L. Metzker. Nature Reviews Genetics 11, 31-46 (January 2010)
  34. 34. Sequencing/Imaging Michael L. Metzker. Nature Reviews Genetics 11, 31-46 (January 2010)
  35. 35. 48
  36. 36. Sequencing tumour genomes Straton et al., Nature. 2009 Apr 9;458(7239):719-24.
  37. 37. Stein LD. The case for cloud computing in genome informatics. Genome Biology 2010, 11:207 (5 May 2010)

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