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:

Too much of a good thing…. Protooncogenes  Oncogenes

Src

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

Alter promoter utilization by METHYLATION

Alter promoter utilization

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

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

Viral driver

Increase the number of copies of a gene

Transcription Translation Increase the amount of mRNA

Increase the amount of mRNA

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

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

DNA Point Mutation

DNA Deletion / Protein Truncation

Chromosomal Translocation

Decrease Turnover

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