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Subset of retinoblastoma tumours is associated with BRCA1/2 mutations

Authors
 Yong Joon Kim  ;  Hyo Song Park  ;  Jeonghwan Youk  ;  Jung Woo Han  ;  Suk Ho Byeon  ;  Sung Soo Kim  ;  Young Seok Ju  ;  Christopher Seungkyu Lee 
Citation
 BRITISH JOURNAL OF OPHTHALMOLOGY, Vol.108(7) : 1011-1017, 2024-07 
Journal Title
BRITISH JOURNAL OF OPHTHALMOLOGY
ISSN
 0007-1161 
Issue Date
2024-07
MeSH
BRCA1 Protein* / genetics ; BRCA2 Protein* / genetics ; Child ; Child, Preschool ; DNA Methylation ; DNA Mutational Analysis ; Female ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Infant ; Male ; Mutation ; Retinal Neoplasms* / genetics ; Retinoblastoma Binding Proteins / genetics ; Retinoblastoma* / genetics ; Retrospective Studies ; Ubiquitin-Protein Ligases ; Whole Genome Sequencing
Keywords
Genetics ; Retina
Abstract
Background We investigated the potential association between pathogenic BRCA1/2 variants and retinoblastoma pathogenicity.Methods In this single-centre, retrospective case series, we performed hereditary cancer panel tests using blood samples for patients with retinoblastoma diagnosed between March 2017 and October 2021. Bioinformatics prediction tools were then used to conduct in silico pathogenicity assessments for patients with BRCA1/2 family variants, in addition to the American College of Medical Genetics and Genomics (ACMG) variant classification. One patient with a germline BRCA1 variant was analysed with whole-genome sequencing (WGS), mutational signature analysis and methylation analysis for RB1 and BRCA using the patient's tumour and blood samples.Results Of 30 retinoblastoma patients who underwent panel sequencing, six (20%) were found to carry germline variants in the BRCA1/2 or BRIP1 genes. Among these six patients, two had pathogenic or likely pathogenic variants as per the ACMG variant classification. Additionally, three patients showed potential pathogenic BRCA1/2 family variants through further analysis with alternative bioinformatics prediction tools. In the WGS analysis of a tumour from a patient with a germline likely pathogenic BRCA1 variant in one allele, we observed the loss of one RB1 allele due to a large deletion. No somatic non-synonymous mutations or frameshift indels were detected in the RB1 locus of the remaining allele. This sample also showed BRCA1 gene promoter hypermethylation in the tumour, indicating additional epigenetic silencing.Conclusion This study demonstrated that some retinoblastoma patients harboured germline BRCA1/2 family variants, which may be associated with the development of retinoblastoma along with RB1 mutations.
Full Text
https://bjo.bmj.com/content/108/7/1011.long
DOI
10.1136/bjo-2023-323388
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sung Soo(김성수) ORCID logo https://orcid.org/0000-0002-0574-7993
Kim, Yong Joon(김용준)
Byeon, Suk Ho(변석호) ORCID logo https://orcid.org/0000-0001-8101-0830
Lee, Christopher Seungkyu(이승규) ORCID logo https://orcid.org/0000-0001-5054-9470
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/201014
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