Retinoblastoma

Abstract

Retinoblastoma (RB) is the most common primary intraocular malignancy of childhood associated with blindness and mortality. Mortality from RB has been significantly reduced with earlier diagnosis and improved methods of treatment. Biallelic inactivation of the tumor suppressor gene, RB1, is the cause of retinoblastoma. Multistep genetic analyses, including DNA sequencing, Southern blot, transcript promoter methylation analysis, and real-time PCR, have been used to characterize potential genetic abnormalities of RB1. Predisposing germline RB1 mutations can be detected in 90-95 % of probands with heritable RB, while the detection rate is about 13 % for individuals with unilateral RB. Due to the presence of low-level mosaicism, chromosome rearrangements, or deep intronic splice site changes, detection of mutations can be challenging. The absence of detectable RB1 mutations in a subset of unilateral RB tumors or in bilateral cases suggests the presence of alternate genetic mechanisms. A subset of unilateral RB tumors is associated with amplification of the MYCN oncogene.