Preliminary results: Comprehensive national retinoblastoma cohort in Finland ‐ RB1 mutation spectrum

Abstract

AbstractPurposeRetinoblastoma (Rb), a malignancy of developing retina, emerges almost always after biallelic mutation and inactivation of tumor suppressor gene RB1. In heritable Rb, a child carries germline RB1 mutation. Identifying this will help in future risk management and family planning. Recently, we have made an effort to create a comprehensive national register for Rb. DNA sequencing for mutations in RB1 is being offered to every patient not previously tested and the results are included in the register.MethodsOf the 226 Rb patients registered in the Finnish Retinoblastoma Register until January 2016, 72 have so far underwent germline DNA testing and 40 patients from 32 unrelated families tested positive for mutation. RB1 mutation detection methods varied depending on the time period. Mutations were checked for pathogenicity from the Leiden Open Variation Database (http://rb1-lsdb.d-lohmann.de).ResultsRB1 mutations comprised 90% of heritable (bilateral, familial or both) Rb and 10% were sporadic unilateral tumors (unifocal or too advanced to assess focality). The distribution of mutation types was 46% nonsense, 15% frameshift, 15% splice site, 3% large indel, 8% missense, 13% chromosomal deletions and none promoter. Two novel mutations (c.1A>C and c.2042_2203+?del) were detected. Five mutations (13%) had been reported only once and nine mutations (23%) three times or less.ConclusionsThe frequencies of the type of mutation in the RB1 gene in the preliminary results of our national cohort expectedly follow the mutation spectrum described worldwide.