1. Introduction to Cancer Genomics
Eva Yap, MSc. Student
Experimental Medicine Graduate Program, BC Cancer Research Centre
February 25, 2016
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 1 / 24

2. Overview
1 Genetic Variations in Oncogenesis
2 Genomics-driven Era of Cancer Research
3 Summary
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 2 / 24

3. Overview
1 Genetic Variations in Oncogenesis
2 Genomics-driven Era of Cancer Research
3 Summary
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 3 / 24

4. Cancer is an (epi)genetic disease
Proto-oncogenes - stimulate proliferation, inhibit differentiation and
apoptosis
Tumour suppressors - inhibit proliferation, stimulate differentiation
and apoptosis
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 4 / 24

5. Cancer is an (epi)genetic disease
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 5 / 24

6. Inherited vs. Acquired
Knudson’s two hit hypothesis, loss of heterozygosity
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 6 / 24

7. Driver vs. Passenger Mutations
Driver mutations confer growth advantage on the cancer cell
Passenger mutations has no functional consequences and occur
during cell division
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 7 / 24

8. Hallmarks of Cancer
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 8 / 24

9. Hallmarks of Cancer
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 9 / 24

10. Types of Mutations
Single nucleotide variants (SNVs)
Structural variants (SVs)
Copy number variations (CNVs)
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 10 / 24

11. Vogelgram and Malignant Transformation of a Polyp
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 11 / 24

12. The Philadelphia Chromosome
BCR-ABL1 transcript codes for a fusion protein that is always on, thereby
causing unregulated cell division.
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 12 / 24

13. EGFR Copy Number Amplification in Lung Cancer
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 13 / 24

14. Overview
1 Genetic Variations in Oncogenesis
2 Genomics-driven Era of Cancer Research
3 Summary
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 14 / 24

15. A Milestone for Genomics
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 15 / 24

16. A Milestone for Genomics
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 16 / 24

17. NGS Workflow
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 17 / 24

18. Different Types of NGS Methods
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 18 / 24

19. Example of a variant calling pipeline
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 19 / 24

20. Not a one-size-fits-all solution
Cancer treatments: surgery, radiation, chemotherapy
Two types of cancers (e.g. eye vs. colorectal vs. blood vs. lung) can
be driven by distinct mutations
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 20 / 24

21. Interpatient Heterogeneity
In fact, within the same type of cancer, interpatient heterogeneity exists!
Lung Adenocarcinoma - 230 samples (TCGA, Nature 2014)
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 21 / 24

22. Targeted therapy
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 22 / 24

23. Overview
1 Genetic Variations in Oncogenesis
2 Genomics-driven Era of Cancer Research
3 Summary
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 23 / 24

24. Take-home messages
Cancer can be driven by various types of genetic mutations
Advancement in genomics can improve our understanding of cancer
biology leading to better patient management and therapeutic
strategy
Eva Yap, MSc. Student (Experimental Medicine Graduate Program, BC Cancer Research Centre)Introduction to Cancer Genomics February 25, 2016 24 / 24