RESUMEN
Although an association between protein-truncating variants and breast cancer risk has been established for 11 genes, only alterations in BRCA1, BRCA2, TP53 and PALB2 have been reported in Asian populations. Given that the age of onset of breast cancer is lower in Asians, it is estimated that inherited predisposition to breast cancer may be more significant. To determine the potential utility of panel testing, we investigated the prevalence of germline alterations in 11 established and 4 likely breast cancer genes in a cross-sectional hospital-based cohort of 108 moderate to high-risk breast cancer patients using targeted next generation sequencing. Twenty patients (19%) were identified to carry deleterious mutations, of whom 13 (12%) were in the BRCA1 or BRCA2, 6 (6%) were in five other known breast cancer predisposition genes and 1 patient had a mutation in both BRCA2 and BARD1. Our study shows that BRCA1 and BRCA2 account for the majority of genetic predisposition to breast cancer in our cohort of Asian women. Although mutations in other known breast cancer genes are found, the functional significance and breast cancer risk have not yet been determined, thus limiting the clinical utility of panel testing in Asian populations.
Asunto(s)
Neoplasias de la Mama/genética , Mutación de Línea Germinal , Adulto , Proteína BRCA1/química , Proteína BRCA1/genética , Proteína BRCA2/química , Proteína BRCA2/genética , Estudios de Cohortes , Estudios Transversales , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Malasia , Linaje , Proteínas Supresoras de Tumor/química , Proteínas Supresoras de Tumor/genética , Ubiquitina-Proteína Ligasas/química , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
MicroRNAs are endogenous ~22nt RNAs that negatively regulate gene expression at the posttranscriptional level via binding to the 3'-untranslated region (3'UTR) of target mRNAs. The microRNA miR-27a was reported to depress the expression of myostatin, a critical inhibitor of skeletal myogenesis, by binding to its 3'UTR in mouse. In this study, we cloned the full-length 3'UTR of porcine myostatin by rapid amplification of 3'-cDNA ends (3'-RACE) and demonstrated that the 3'UTR of porcine myostatin is targeted by miR-27a. The phenomenon that the level of myostatin inversely correlated with miR-27a was observed in fat and heart of pigs and also in proliferating porcine myoblasts. Besides, overexpression of miR-27a in porcine myoblasts promoted cell proliferation by reducing the expression of myostatin. Our data suggest that miR-27a positive regulates porcine myoblast proliferation via targeting myostatin.
