1. Introduction to cancer
genetics 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

4. Mutations: Somatic and Germline
Somatic mutations Germline mutations
Occur in nongermline tissues Present in egg or sperm
Are nonheritable Are heritable
Cause cancer family syndrome
Nonheritable
Somatic mutation Mutation in All cells
(e.g., breast) egg or sperm affected in
offspring

6. Hallmarks of Cancer
Hanahan & Weinberg. Cell. 2000 Jan 7;100(1):57-70

7. Hallmarks of Cancer
Hanahan & Weinberg. Cell. 2000 Jan 7;100(1):57-70

8. Genomic and epigenomic aberrations in cancer

9. High-throughput technologies to identify cancer alterations

10. Expression microarrays

13. Comparative Genomics Hybridization (CGH)

14. Comparative Genomics Hybridization (CGH)

16. DNA Sequencing
Science 13 October 2006

17. Sjoblom et al., Science 2006

18. Detecting the Troublemakers

19. Drivers vs Passengers
Straton et al., Nature. 2009 Apr 9;458(7239):719-24.

20. Cancer genome characterization
Chin and Gray. Nature 452, 553-563(3 April 2008)

21. Chin and Gray. Nature 452, 553-563(3 April 2008)

22. Various alterations affecting
the same pathway
Chin and Gray. Nature 452, 553-563(3 April 2008)

23. Molecular Diagnostics of Cancer
Laura J. van 't Veer & René Bernards. Nature 452, 564-570(3 April 2008)

24. Generating a prognostic gene-
expression signature
Laura J. van 't Veer & René Bernards. Nature 452, 564-570(3 April 2008)

27. 70 gene prognostic signature in breast cancer
Text
Laura J. van 't Veer, et al. Nature 415, 530-536(31 January 2002)

28. 70 gene prognostic signature in breast cancer
Text
Laura J. van 't Veer, et al. Nature 415, 530-536(31 January 2002)

29. 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

30. Oncotype DX: 21 gene signature in breast cancer for
predicting distance recurrence
Distant 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.

31. Oncotype DX: 21 gene signature in breast cancer for
predicting distance recurrence
Recurrence Score in N-, ER+ patients
1) Paik et al NEJM 2004, 2) Habel et al Breast Cancer Research 2006
3) Paik et al JCO 2006, 4) Gianni et al JCO 2005

33. Next Generation Sequencing Revolution
Straton et al., Nature. 2009 Apr 9;458(7239):719-24.

34. Template preparation
Sequencing
Imaging
Data processing

35. Template preparation
Clonally amplified templates from a single DNA molecule
Emulsion PCR
Solid Phase Amplification
Single DNA molecule
Primer immobilized
Template immobilized
Polymerase immobilized

36. 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)

37. 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)

38. 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)

39. 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)

40. Sequencing/Imaging
Michael L. Metzker. Nature Reviews Genetics 11, 31-46 (January 2010)

41. Sequencing/Imaging

42. Sequencing/Imaging
Michael L. Metzker. Nature Reviews Genetics 11, 31-46 (January 2010)

43. Sequencing/Imaging
Michael L. Metzker. Nature Reviews Genetics 11, 31-46 (January 2010)

45. 48

46. Sequencing tumour genomes
Straton et al., Nature. 2009 Apr 9;458(7239):719-24.

49. Stein LD. The case for cloud computing in genome informatics. Genome Biology 2010, 11:207 (5 May 2010)