Molecular Genetics of RB1 ——The Retinoblastoma Gene

Thirty-seven years ago Alfred Knudson proposed his "two-hit" theory of the molecular etiology of retinoblastoma, establishing an elegant conceptual paradigm for tumorigenesis in general. A great body of work has subsequently elucidated the structure and function of the RB1 gene and the biology of its protein product, pRB. Multiple categories of mutations have been characterized and correlated with phenotypic expression, including translocations, deletions, insertions, and point mutations. The purpose of this review is to provide a concise overview of the molecular genetics and genotype-phenotype correlations in retinoblastoma.