Ch 16 - Cancer Genetics and Genomics

Driver Gene Mutations

mutations that cause cancer to develop, some specific to certain cancers other more general call proliferation

Passenger Gene Mutations

mutations further along in the development of cancer, not directly causing it, along for the ride, appears as cancer develops (not before)

Normal genetic pathways

genome to epigenome to gene expression

• negative feedback to ensure normal homeostasis

Genetic pathways associated with cancer

loss of genomic integrity or abnormal epigenome profile or disordered copy number and gene expression

• positive feedback of progressively more disordered gene expression and genome integrity

Two types of driver genes

• protooncogenes

• tumor supressor genes

Protooncogenes

genes involved in normal cell division or proliferation that may become activated by mutation to become an oncogene

• “gas pedal”

• acts in dominant allele manner

• gain of function

Tumor Supressor Genes (TSGs)

genes involved in the regulation of the cell cycle

• “brake pedal”

• acts in recessive allele manner

• loss of function

Hereditary Cancer Syndromes

forms of cancer with a higher incidence in relatives of people with cancer than in the general population

• often due primarily to inheritance of a single mutant gene with high penetrance

Two-Hit Theory of TSG

The hypothesis that two mutations are required in tumor suppressor genes to cause cancer, emphasizing the need for both alleles to be inactivated for tumor growth

Why does retinoblastoma appear to have dominant inheritance

individuals inherit the 1st hit and are highly likely to get 2nd hit

• tumor development early in life

Gene expressoin profile

measurement of mRNA expression in a sample of tissue

• multiple genes can be associated with a specific cancer, determine which one to best determine treatment

environmental impact on cancer

food, natural + artificial radiation, chemicals, viruses, bacteria

• increase risk for cancer

Radiation

ionizing radiation from background radiation and medical exposure is known to increase risk for cancer

chemical carcinogens

tobacco, components of diet, industrial carcinogens, toxic wastes