Molecular Genetics Mutations of Retinoblastoma

Abstract

Retinoblastoma is a cancer that arises because both copies of the RB1 gene that normally suppresses retinoblastoma are lost from a developing retinal cell in fetuses, babies, and young children. Retinoblastoma is the prototype genetic cancer in one or both eyes of young children, most retinoblastomas are initiated by bial­lelic mutation of the retinoblastoma tumor suppressor gene, RB1, in a developing retinal cell. All those with bilateral retinoblastoma have heri­table cancer, although 95% have not inherited the RB1 mutation. Non­heritable retinoblastoma is always unilateral, with 98% caused by loss of both RB1 alleles from the tumor, whereas 2% have normal RB1 in tumors initiated by amplification of the MYCN oncogene. A rare subset of retinoblastoma is initiated by somatic amplification of the MYCN oncogene in a predisposing retinal cell. The retinoblastoma protein (pRB), encoded by RB1, is an important transcription factor.