Heterogenic Loss of BRCA in Breast Cancer: The “Two-Hit” Hypothesis Takes a Hit

Excerpt

Most hereditary cancers have been linked to mutations in tumor suppressor genes. The first tumor suppressor to be cloned was the retinoblastoma gene, RB1. Retinoblastoma occurs in both hereditary and nonhereditary forms. In the hereditary form, most children with an affected parent develop bilateral retinoblastoma; however, some develop unilateral retinoblastoma, and others are not affected themselves, but have an affected child. These findings led to the theory that a single mutation is not sufficient for tumorigenesis. Alfred Knudson hypothesized that hereditary retinoblastoma involves two mutations, one in the germ line, whereas nonhereditary retinoblastoma is due to two somatic mutations, a hypothesis known as Knudson’s “two-hit” hypothesis.1 …