Whole-Genome Sequencing of Retinoblastoma Reveals the Diversity of Rearrangements Disrupting <i>RB1</i> and Uncovers a Treatment-Related Mutational Signature.

ABSTRACT: The development of retinoblastoma is thought to require pathological genetic changes in both alleles of the RB1 gene. However, cases exist where RB1 mutations are undetectable, suggesting alternative pathways to malignancy. We used whole-genome sequencing (WGS) and transcriptomics to investigate the landscape of sporadic retinoblastomas derived from twenty patients, sought RB1 and other driver mutations and investigated mutational signatures. At least one RB1 mutation was identified in all retinoblastomas, including new mutations in addition to those previously identified by clinical screening. Ten tumours carried structural rearrangements involving RB1 ranging from relatively simple to extremely complex rearrangement patterns, including a chromothripsis-

SUBMITTER: Davies HR 

PROVIDER: S-EPMC7918943 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature