BRCA1 and BRCA2 whole cDNA analysis in unsolved hereditary breast/ovarian cancer patients.
Cancer Genet
; 258-259: 10-17, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34237702
ABSTRACT
Germline pathogenic variants in BRCA1 and BRCA2 genes (BRCA1/2) explain an important fraction of hereditary breast/ovarian cancer (HBOC) cases. Genetic testing generally involves examining coding regions and exon/intron boundaries, thus the frequency of deleterious variants in non-coding regions is unknown. Here we analysed BRCA1/2 whole cDNA in a large cohort of 320 unsolved high-risk HBOC cases in order to identify potential splicing alterations explained by variants in BRCA1/2 deep intronic regions. Whole RNA splicing profiles were analysed by RT-PCR using Sanger sequencing or high-resolution electrophoresis in a QIAxcel instrument. Known predominant BRCA1/2 alternative splicing events were detected, together with two novel events BRCA1 â¼21 and BRCA2 Δ18q_27p. BRCA2 exon 3 skipping was detected in one patient (male) affected with breast cancer, caused by a known Portuguese founder mutation (c.156_157insAluYa5). An altered BRCA2 splicing pattern was detected in three patients, consisting in the up-regulation of â¼20A, Δ22 and â¼20A+Δ22 transcripts. In silico analysis and semi-quantitative data identified the polymorphism BRCA2 c.8755-66T>C as a potential modifier of Δ22 levels. Our findings suggest that mRNA alterations in BRCA1/2 caused by deep intronic variants are rare in Spanish population. However, RNA analysis complements DNA-based strategies allowing the identification of alterations that could go undetected by conventional testing.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA Complementar
/
Proteína BRCA1
/
Predisposição Genética para Doença
/
Proteína BRCA2
/
Síndrome Hereditária de Câncer de Mama e Ovário
/
Mutação
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Cancer Genet
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Espanha