The genomic landscape of familial glioma.
Sci Adv
; 9(17): eade2675, 2023 04 28.
Article
em En
| MEDLINE
| ID: mdl-37115922
ABSTRACT
Glioma is a rare brain tumor with a poor prognosis. Familial glioma is a subset of glioma with a strong genetic predisposition that accounts for approximately 5% of glioma cases. We performed whole-genome sequencing on an exploratory cohort of 203 individuals from 189 families with a history of familial glioma and an additional validation cohort of 122 individuals from 115 families. We found significant enrichment of rare deleterious variants of seven genes in both cohorts, and the most significantly enriched gene was HERC2 (P = 0.0006). Furthermore, we identified rare noncoding variants in both cohorts that were predicted to affect transcription factor binding sites or cause cryptic splicing. Last, we selected a subset of discovered genes for validation by CRISPR knockdown screening and found that DMBT1, HP1BP3, and ZCH7B3 have profound impacts on proliferation. This study performs comprehensive surveillance of the genomic landscape of familial glioma.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
/
Glioma
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos