Common 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