8.2 genetic basis and hallmarks of cancer

what is cancer caused by

changes to our genes → the gene that control cell growth and division

how can genetic changes arise from

• environmental factors

  • virus infection

  • chemical exposure

  • radiation

• errors in cell division

• inherited mutations

what is the flow of accumulation of mutations to lead to cancer

1. first mutation → alters cell cycle control: giving the cell its descendants a selective advantage for proliferation

2. second mutation → further damages cell cycle control + increases selective advantages for proliferation among descendants of the cell

3. third mutation → accumulation of this: proliferation is notably abnormal

4. fourth - fifth mutation → most malignant tumors form: affects proliferation, cell death and life span

what are the 2 classes of genes implicated in cancers

1) proto-oncogenes (‘accelerators’)

• promote cell growth, division and survival under appropriate conditions

• in cancer: these genes are permanently activated → ‘gain of function’

  • cells receives continuous grow signal regardless of conditions

• mutated form is called oncogenes

• egs: Ras, Myc, Cyclin D, EGFR, HER2

2) tumor suppressor genes (‘brakes’)

• prevent cell proliferation, repair DNA damage or regulate apoptosis

• in cancer: these genes are lost or inactivated → ‘loss of function’

  • when both copies are lost, cell is no longer able to suppress growth

• egs: Rb, p53, PTEN, APC, BRCA1, BRCA2

what is somatic mutations

an alteration in DNA that occurs in body cells after conception, caused by errors in DNA replication and repair, or damage from free radicals produced by normal metabolism

what is the difference between inherited mutations and somatic mutations

inherited mutations are passed through the germ-line, and is thus present in every cell of the body, and thus individuals with a genetic pre-disposition are at a much greater risk of developing cancer

germ-line: the sperm cell and/or egg cell

what are the genes that would be affected in heritable mutations

usually in the tumor suppressor gene