1. Have a positive role in cell division Have a negative role in cell division Have a role in the maintenance of DNA integrity Genes altered in cancer typically:

2. Too much of a good thing…. Protooncogenes  Oncogenes

5. Src

7. Conversion of a Proto- oncogene  an Oncogene Change gene Expression / Protein Production

8. Alter promoter utilization by METHYLATION

9. Alter promoter utilization

10. Frequency of TERT promoter mutations in human cancers. Abstract Reactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechanisms remain poorly understood. Here we report the presence of recurrent somatic mutations in the TERT promoter in cancers of the central nervous system (43%), bladder (59%), thyroid (follicular cell-derived, 10%) and skin (melanoma, 29%). In thyroid cancers, the presence of TERT promoter mutations (when occurring together with BRAF mutations) is significantly associated with higher TERT mRNA expression, and in glioblastoma we find a trend for increased telomerase expression in cases harbouring TERT promoter mutations. Both in thyroid cancers and glioblastoma, TERT promoter mutations are significantly associated with older age of the patients. Our results show that TERT promoter mutations are relatively frequent in specific types of human cancers, where they lead to enhanced expression of telomerase. Nat Commun.Nat Commun. 2013;4:2185. Alter promoter utilization by POINT MUTATION

11. Alter promoter by TRANSLOCATION Chromosome 14 with translocation Chromosome 8 with translocation

12. Viral driver

13. Increase the number of copies of a gene

15. Transcription Translation Increase the amount of mRNA

16. Increase the amount of mRNA

17. Promoter mis-use Decreased Methylation Point Mutation Translocation Viral Expression Increase copy number In DNA Of RNA/Protein Increase protein production by: :

18. Conversion of a Proto- oncogene  an Oncogene Change the function of a gene product

19. DNA Point Mutation

20. DNA Deletion / Protein Truncation

21. Chromosomal Translocation

22. Decrease Turnover

23. Advantageous DNA mutation Point mutation Deletion/truncation Creation of a fusion protein Decrease protein turnover Inhibit destruction Increase protein activity by: :