[Perspective] The cancer predisposition revolution

Studies of rare cancer predisposition syndromes often lead to the identification of genes critical to carcinogenesis. In 1969, Li and Fraumeni described a constellation of various cancers in the family members of four unrelated children who were diagnosed with soft tissue sarcomas (1). They posited that the cancers best fit an autosomal dominant pattern of inheritance, attributable to a genetic defect. At that time, cancer was not generally thought of as a genetic disease. Their hypothesis set the stage for establishing germline mutations in the tumor suppressor gene TP53 as the underlying genetic event in Li-Fraumeni syndrome (LFS) families (2) (see the figure). It also foreshadowed dozens of discoveries, still ongoing, that associate mutations in tumor suppressor genes, activated oncogenes, mitochondrial genes, and DNA repair genes with cancer predisposition phenotypes in which multiple different neoplasms occur across generations. Authors: David Malkin, Judy E. Garber, Louise C. Strong, Stephen H. Friend
Source: ScienceNOW - Category: Science Authors: Tags: Cancer Source Type: news