Tumor-suppressor genes that escape from X-inactivation contribute to cancer sex bias.
Nat Genet
; 49(1): 10-16, 2017 01.
Article
en En
| MEDLINE
| ID: mdl-27869828
ABSTRACT
There is a striking and unexplained male predominance across many cancer types. A subset of X-chromosome genes can escape X-inactivation, which would protect females from complete functional loss by a single mutation. To identify putative 'escape from X-inactivation tumor-suppressor' (EXITS) genes, we examined somatic alterations from >4,100 cancers across 21 tumor types for sex bias. Six of 783 non-pseudoautosomal region (PAR) X-chromosome genes (ATRX, CNKSR2, DDX3X, KDM5C, KDM6A, and MAGEC3) harbored loss-of-function mutations more frequently in males (based on a false discovery rate < 0.1), in comparison to zero of 18,055 autosomal and PAR genes (Fisher's exact P < 0.0001). Male-biased mutations in genes that escape X-inactivation were observed in combined analysis across many cancers and in several individual tumor types, suggesting a generalized phenomenon. We conclude that biallelic expression of EXITS genes in females explains a portion of the reduced cancer incidence in females as compared to males across a variety of tumor types.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Genes Supresores de Tumor
/
Cromosomas Humanos X
/
Inactivación del Cromosoma X
/
Genes Ligados a X
/
Sexismo
/
Mutación
/
Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos