The “two hit” model of carcinogenesis invented by Alfred K. Knudson to explain clinical-epidemiological observations on retinoblastoma (q.v.). This revolutionary concept proposed that certain cancers were caused, not by the presence of an oncogene, but by the absence of an anti-oncogene. In the case of retinoblastoma, children with both eyes affected had a germ-line mutation that predisposed them to the disease. However, a second “hit” or mutation was needed to produce the cancer. Patients without the germ-line mutation required two hits. Extra time was required to acquire the first of the two mutations, and so children with hereditary retinoblastoma developed the disease in both eyes or at multiple sites in one eye, whereas children lacking the RB gene developed single tumors and at a later age. See Chronology, 1971, Knudson.
Subjects: Genetics and Genomics — Chemistry.