Non-RB1 germline cancer predisposing variants found in retinoblastoma patients

Abstract

PurposeIt is well known that individuals with hereditary retinoblastoma are at lifelong high risk for developing subsequent malignant neoplasms (SMN). However, the role that non-RB1 germline variants play in tumorigenesis and SMN risk has not yet been studied. The purpose of this study is to report the frequency and spectrum of non-RB1 germline cancer predisposing variants in individuals with retinoblastoma (RB). MethodsRetrospective data collection from institutional electronic medical records of 94 individuals seen at our institution with personal history of retinoblastoma, who had undergone next-generation sequencing germline analysis. ResultsThe prevalence of individuals with cancer predisposition was 57%, of which 45% had a pathogenic/likely pathogenic in the RB1 gene, 12% harbored a pathogenic/likely pathogenic variant in a non-RB1 gene, and 7% had both. No difference was found between patients with and without non-RB1 variants when comparing demographic and clinical characteristics, including time to SMN. Variants were found in 7 different genes, with only 1 variant repeating 3 times. ConclusionIn this small cohort of patients with retinoblastoma, non-RB1 variants did not appear to augment tumorigenesis or disease progression. Larger studies are required to determine associations between specific variants and development of SMN.