Oncogenes

Proto-oncogenes (tumor promoters)

• ABL: Chronic myeloid leukemia
• ALK: Large cell lymphoma, non–small cell lung cancer
• BRAF: Melanoma
  • RAF is rapidly accelerated fibrosarcoma
• BCL-2: [Non-Hodgkin lymphomas|Follicular lymphoma], Diffuse large B cell lymphoma
  • BCL-2 mutations are associated with diffuse large B-cell lymphoma.
• HER1: Squamous cell lung cancer
• HER2/neu: Breast cancer, ovarian cancer
• JAK2: Chronic myeloproliferative disorders.
  • Polycythemia Vera (PV) (~95% of cases).
  • Essential Thrombocythemia (ET) (~50% of cases).
  • Primary Myelofibrosis (MF) (~50% of cases).
• MYC: Neuroblastoma (NMYC), small cell lung cancer (LMYC), Burkitt lymphoma
• RET: Medullary thyroid cancer, pheochromocytoma
  • Mutations are associated with MEN2
• KRAS: Colorectal, lung, pancreatic cancers
  • EGFR leads to downstream activation of KRAS.
  • Signal transducer in MAP-kinase pathway (Growth factors).
  • Active = GTP-bound.
  • Inactive = GDP-bound.
  • Inactivation requires intrinsic GTPase activity (helped by GAPs).
  • Defect: Point mutation disables GTPase activity → Ras stays GTP-bound (constitutively active).

Anti-oncogenes (tumor suppressors)

• APC/β catenin: Colorectal cancer, pancreatic cancer
• BRCA1, BRCA2: Breast cancer, ovarian cancer
  • Involved in repair of double-stranded DNA breaks
• NF1: Neuroblastoma, sarcoma
• RB (RB1): Retinoblastoma, osteosarcoma
  • Retinoblastoma protein (Rb protein): causes cell cycle arrest at the G1 phase by inhibiting E2F transcription factor.
  • Needs to be phosphorylated (rendering it inactive) to allow progression through the G1/S checkpoint
• TP53: Most cancers, Li-Fraumeni (SBLA) syndrome (multiple malignancies at early age; Sarcoma, Breast/Brain, Lung/Leukemia, Adrenal gland)
  • Encodes the p53 protein that suppresses cell division and regulates DNA repair and apoptosis.
• VHL: Renal cell cancer
• WT1: Wilms tumor