A deep intronic recurrent CHEK2 variant c.1009-118_1009-87delinsC affects pre-mRNA splicing and contributes to hereditary breast cancer predisposition.
Breast
; 75: 103721, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38554551
ABSTRACT
Germline CHEK2 pathogenic variants confer an increased risk of female breast cancer (FBC). Here we describe a recurrent germline intronic variant c.1009-118_1009-87delinsC, which showed a splice acceptor shift in RNA analysis, introducing a premature stop codon (p.Tyr337PhefsTer37). The variant was found in 21/10,204 (0.21%) Czech FBC patients compared to 1/3250 (0.03%) controls (p = 0.04) and in 4/3639 (0.11%) FBC patients from an independent German dataset. In addition, we found this variant in 5/2966 (0.17%) Czech (but none of the 443 German) ovarian cancer patients, three of whom developed early-onset tumors. Based on these observations, we classified this variant as likely pathogenic.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Íntrons
/
Splicing de RNA
/
Mutação em Linhagem Germinativa
/
Predisposição Genética para Doença
/
Quinase do Ponto de Checagem 2
Limite:
Adult
/
Female
/
Humans
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Breast
Assunto da revista:
ENDOCRINOLOGIA
/
NEOPLASIAS
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
República Tcheca