• Like
Introduction cancer genetics and genomics
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

Introduction cancer genetics and genomics

  • 931 views
Published

 

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
No Downloads

Views

Total Views
931
On SlideShare
0
From Embeds
0
Number of Embeds
0

Actions

Shares
Downloads
67
Comments
0
Likes
1

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide

Transcript

  • 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. 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. Hallmarks of Cancer Hanahan & Weinberg. Cell. 2000 Jan 7;100(1):57-70
  • 4. Hallmarks of Cancer Hanahan & Weinberg. Cell. 2000 Jan 7;100(1):57-70
  • 5. Genomic and epigenomic aberrations in cancer
  • 6. High-throughput technologies to identify cancer alterations
  • 7. Expression microarrays
  • 8. Comparative Genomics Hybridization (CGH)
  • 9. Comparative Genomics Hybridization (CGH)
  • 10. DNA Sequencing Science 13 October 2006
  • 11. Sjoblom et al., Science 2006
  • 12. Detecting the Troublemakers
  • 13. Drivers vs Passengers Straton et al., Nature. 2009 Apr 9;458(7239):719-24.
  • 14. Cancer genome characterization Chin and Gray. Nature 452, 553-563(3 April 2008)
  • 15. Chin and Gray. Nature 452, 553-563(3 April 2008)
  • 16. Various alterations affecting the same pathway Chin and Gray. Nature 452, 553-563(3 April 2008)
  • 17. Molecular Diagnostics of Cancer Laura J. van t Veer & René Bernards. Nature 452, 564-570(3 April 2008)
  • 18. Generating a prognostic gene- expression signature Laura J. van t Veer & René Bernards. Nature 452, 564-570(3 April 2008)
  • 19. 70 gene prognostic signature in breast cancer Text Laura J. van t Veer, et al. Nature 415, 530-536(31 January 2002)
  • 20. 70 gene prognostic signature in breast cancer Text Laura J. van t Veer, et al. Nature 415, 530-536(31 January 2002)
  • 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. 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. 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. Next Generation Sequencing Revolution Straton et al., Nature. 2009 Apr 9;458(7239):719-24.
  • 25. Template preparationSequencingImagingData processing
  • 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. 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. 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. 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. 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. Sequencing/ImagingMichael L. Metzker. Nature Reviews Genetics 11, 31-46 (January 2010)
  • 32. Sequencing/Imaging
  • 33. Sequencing/ImagingMichael L. Metzker. Nature Reviews Genetics 11, 31-46 (January 2010)
  • 34. Sequencing/Imaging Michael L. Metzker. Nature Reviews Genetics 11, 31-46 (January 2010)
  • 35. 48
  • 36. Sequencing tumour genomes Straton et al., Nature. 2009 Apr 9;458(7239):719-24.
  • 37. Stein LD. The case for cloud computing in genome informatics. Genome Biology 2010, 11:207 (5 May 2010)