Diverse mutational spectrum in the 13q14 chromosomal region in a Brazilian cohort of retinoblastoma.

Autor: Mendonça V; Genetics Program, Instituto Nacional de Câncer, Rio de Janeiro, Brazil; Genetics Department, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: vanessa.mendonca@inca.gov.br., Pereira Sena P; Genetics Program, Instituto Nacional de Câncer, Rio de Janeiro, Brazil; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany., Evangelista Dos Santos AC; Genetics Program, Instituto Nacional de Câncer, Rio de Janeiro, Brazil., Rodrigues Bonvicino C; Genetics Program, Instituto Nacional de Câncer, Rio de Janeiro, Brazil., Ashton-Prolla P; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil., Epelman S; Pediatric Oncology Service, Hospital Santa Marcelina, São Paulo, Brazil., Ferman SE; Department of Pediatric Oncology, Clinical Division, Instituto Nacional de Câncer, Rio de Janeiro, Brazil., Lapunzina P; INGEMM, Hospital La Paz, Universidad de Madrid, Madrid, Spain; CIBERER (Centro de Investigación Médica en Red de Enfermedades Raras), Madrid, Spain; ITHACA-European Reference Network, Hospital La Paz, Madrid, Spain., Nevado J; INGEMM, Hospital La Paz, Universidad de Madrid, Madrid, Spain; CIBERER (Centro de Investigación Médica en Red de Enfermedades Raras), Madrid, Spain; ITHACA-European Reference Network, Hospital La Paz, Madrid, Spain., Grigorovski N; Department of Pediatric Oncology, Clinical Division, Instituto Nacional de Câncer, Rio de Janeiro, Brazil., Mattosinho C; Department of Ocular Oncology, Division of Surgery, Instituto Nacional de Câncer, Rio de Janeiro, Brazil., Seuànez H; Genetics Program, Instituto Nacional de Câncer, Rio de Janeiro, Brazil; Genetics Department, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Regla Vargas F; Birth Defects Epidemiology Laboratory, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil; Department of Genetics and Molecular Biology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Jazyk: angličtina
Zdroj: Experimental eye research [Exp Eye Res] 2022 Nov; Vol. 224, pp. 109211. Date of Electronic Publication: 2022 Aug 17.
DOI: 10.1016/j.exer.2022.109211
Abstrakt: Retinoblastoma is a rare childhood tumor caused by the inactivation of both copies of the RB1 gene. Early diagnosis and identification of heritable RB1 mutation carriers can improve the disease outcome and management via genetic counseling. We used the Multiplex Ligation-dependent Probe Amplification (MLPA) method to analyze the RB1 gene and flanking regions in blood samples from 159 retinoblastoma patients previously negative for RB1 point mutations via Sanger sequencing. We detected a wide spectrum of germline chromosomal alterations, ranging from partial loss or duplication of RB1 to large deletions spanning RB1 and adjacent genes. Mutations were validated via karyotyping, fluorescent in situ hybridization (FISH), SNP-arrays (Single Nucleotide Polymorphism-arrays) and/or quantitative relative real-time PCR. Patients with leukocoria as a presenting symptom showed reduced death rate (p = 0.013) and this sign occurred more frequently among carriers of two breakpoints within RB1 (p = 0.05). All unilateral cases presented both breakpoints outside of RB1 (p = 0.0075). Patients with one breakpoint within RB1 were diagnosed at earlier ages (p = 0.017). Our findings characterize the mutational spectrum of a Brazilian cohort of retinoblastoma patients and point to a possible relationship between the mutation breakpoint location and tumor outcome, contributing to a better prospect of the genotype/phenotype correlation and adding to the wide diversity of germline mutations involving RB1 and adjacent regions in retinoblastoma.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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