TY - CHAP M1 - Book, Section TI - Genomic Stability and DNA Repair A1 - Laflamme, Guillaume A1 - Benslimane, Yahya A1 - D’Amours, Damien A2 - Harrington, Lea A. A2 - Tannock, Ian F. A2 - Hill, Richard P. A2 - Cescon, David W. Y1 - 2021 N1 - T2 - The Basic Science of Oncology, 6e AB - There is overwhelming evidence that mutations can cause cancer. Major evidence for the genetic origin of cancer includes (1) the observation of Ames that many carcinogens are also mutagens (Ames et al, 1981) and (2) the finding that genetically determined traits associated with a deficiency in the enzymes necessary to repair lesions in DNA are associated with an increased risk of cancer. Mutations may occur in the germline of an individual and be represented in every cell in the body, or they may occur in a single somatic cell and be identified in a tumor following clonal proliferation. As described in Chapter 7, all species have numerous genes called cellular oncogenes (or proto-oncogenes), many of which are homologous to the transforming oncogenes carried by specific RNA retroviruses. Some human tumors have mutations in these oncogenes that may have led to their activation. However, there is no evidence for germline mutations in cellular oncogenes, perhaps because such mutations in the germline are lethal even in the heterozygous state. In contrast, there is good evidence for germline mutations affecting tumor-suppressor genes, which can lead to familial clustering of cancer or transmission of predisposition to tumors. In such cases, the loss of function of a tumor-suppressor gene is inherited in a Mendelian manner. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - accessbiomedicalscience.mhmedical.com/content.aspx?aid=1179324166 ER -