Overview Mechanism gain of function mutation in a proto-oncogene due to novel protein function only one allele change needed for neoplasia Categories of proto-oncogenes growth factor overproduction growth factor receptor upregulation e.g., HER2/neu signal transducer e.g., ras cell cycle regulators Examples Oncogene Gene Associated Tumor Mechanism BCR:ABL CML 9;22 translocation BCL-2 Follicular and undifferentiated lymphomas 14;18 translocation CCND1 Mantle cell lymphomas 11;14 translocation C-Myc Burkitt's lymphoma 8;14 translocation L-Myc Lung tumor amplification N-MYC Neuroblastoma amplification ERB-B2 Breast, ovarian, and gastric carcinomas amplification CDK4 Melanoma amplification RET Multiple endocrine neoplasia IIA and B point mutation C-KIT Gastrointestinal stromal tumor (GIST) point mutation RAS Colon carcinoma point mutation