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Chapter 079. Cancer Genetics (Part 6)

Oncogenes in Human Cancer Oncogenes of the kind found in human cancers were initially discovered through their presence in the genome of retroviruses capable of causing cancers in chickens, mice, and rats. The cellular homologues of these viral genes are often targets of mutation or aberrant regulation in human cancer. Whereas many oncogenes were discovered because of their presence in retroviruses, other oncogenes, particularly those involved in translocations characteristic of particular leukemias and lymphomas, were isolated through genomic approaches. Investigators cloned the sequences surrounding the chromosomal translocations observed cytogenetically and then deduced the nature of the genes that were. | Chapter 079. Cancer Genetics Part 6 Oncogenes in Human Cancer Oncogenes of the kind found in human cancers were initially discovered through their presence in the genome of retroviruses capable of causing cancers in chickens mice and rats. The cellular homologues of these viral genes are often targets of mutation or aberrant regulation in human cancer. Whereas many oncogenes were discovered because of their presence in retroviruses other oncogenes particularly those involved in translocations characteristic of particular leukemias and lymphomas were isolated through genomic approaches. Investigators cloned the sequences surrounding the chromosomal translocations observed cytogenetically and then deduced the nature of the genes that were the targets of these translocations see below . Some of these were oncogenes known from retroviruses like ABL involved in chronic myelogenous leukemia CML while others were new like BCL2 involved in B cell lymphoma . In the normal cellular environment protooncogenes have crucial roles in cell proliferation and differentiation. Table 79-2 is a partial list of oncogenes known to be involved in human cancer. Table 79-2 Common Oncogenes Altered in Human Cancers ne Oncoge Function Alteration in Cancer Neoplasm AKT1 Serine threoni ne kinase Amplification Gastric carcinoma AKT2 Serine threoni ne kinase Amplification Ovarian breast pancreas cancer BRAF Serine threoni ne kinase Point mutation Melanoma lung colorectal cancer CTNNB1 Signal transduction Point mutation Colon prostate melanoma skin others FOS Transcription factor Overexpressi on Osteosarcomas ERBB2 Receptor tyrosine kinase Point mutation amplification Breast ovary stomach neuroblastoma JUN Transcription factor Overexpressi on Lung cancer MET Receptor tyrosine kinase Point mutation rearrangement Osteocarcinom a kidney glioma MYB Transcription factor Amplification AML CML colon cancer