Preparatory Mindset

Study this chapter with focus on how genetic principles affect clinical practice.

Core Concepts

• Cancer as genetic disease: Cancer results from accumulation of genetic mutations in somatic cells


• Oncogenes: Mutant alleles of proto-oncogenes that PROMOTE growth. Gain-of-function. One hit sufficient.


• Tumor suppressor genes (TSGs) : Genes that normally INHIBIT growth. Loss-of-function. Both copies must be lost (Knudson two-hit hypothesis)


• Knudson two-hit hypothesis: Both alleles of a TSG must be inactivated for cancer to develop


• Philadelphia chromosome: t(9;22) → BCR-ABL fusion → CML. First cytogenetic abnormality linked to cancer.


• Hereditary cancer syndromes: Inherited mutations in TSGs → increased cancer risk (e.g., BRCA1/2 → breast/ovarian, RB1 → retinoblastoma)


• DNA repair genes: Defects → increased mutation rate throughout genome → cancer predisposition

High-Yield Points

• Oncogenes: gain-of-function (one hit); TSGs: loss-of-function (two hits)


• Two-hit hypothesis: inherited mutation (first hit) + somatic mutation (second hit)


• Most cancers are sporadic (somatic mutations), not hereditary

Topic Summary

Cancer is a genetic disease of somatic cells. Oncogenes promote growth; tumor suppressor genes inhibit it. The two-hit hypothesis explains TSG inactivation.