Important Oncogenic Mutations

Question 1

Translocations assoc. w/hematologic malignancies

Answer 1

• Burkitt’s lymphoma = t(8;14)
  
  • 8 = c-myc
  • 14 = IgG heavy chain locus
  • ==> overexpression of c-myc
• CML = t(9;22)
  
  • BCR-ABL fusion ==> increased tyrosine kinase activity
• Mantle Cell lymphoma = t(11;14)
  
  • 11 = cyclin D1
• Follicular lymphoma = t(14;18)
  
  • 18 = BCL2 ==> inhibits apoptosis
• AML (acute pro-myelocytic leukemia) = t(15;17)
  
  • 17 = retinoic acid receptor

Question 2

Common proto-oncogenes + gene product + associated cancer

Answer 2

• RAS = GTP-binding protein
  
  • Choliangiocarcinoma
• MYC = transcription factor
  
  • Burkitt’s Lymphoma
• ERBB-1 (EGFR) = receptor tyrosine kinase
  
  • Lung adenocarcinoma
• ERBB-2 (HER2) = receptor tyrosine kinase
  
  • Breast Cancer
• ABL = nonreceptor tyrosine kinase
  
  • chronic myelogenous leukemia
• BRAF = RAS signal transduction
  
  • Hairy cell leukemia
  • melanoma

Question 3

Common tumor-suppressor genes + gene product + associated cancer

Answer 3

• BRCA-1, BRCA-2 = DNA repair gene
  
  • Breat & Ovarian cancer
• APC/B-catenin = WNT signaling
  
  • colorectal, gastric, pancreatic cancer
  • FAP
• TP53 = genomic stability
  
  • most cancers
  • Li-Fraumeni
• Rb = inhibits G1/S transition
  
  • Retinoblastoma
  • Osteosarcoma
• WT1 = urogenital differentiation
  
  • Wilm’s tumor
• VHL = ubiquitin ligase component
  
  • von-hippel lindau

Question 4

JAK2 Kinase Mutation ==>

Answer 4

• Myeloproliferative disorders:
  
  • Polycythemia Vera
  • Essential Thrombocythemia
  • Myelofibrosis