Revisiting Non-BRCA1/2 Familial Whole Exome Sequencing Datasets Implicates NCK1 as a Cancer Gene.

摘要: Through linkage and candidate gene screening, many breast cancer (BC) predisposition genes have been identified in the past 20 years. However, majority of genetic risks that contribute to familial BC remains undetermined. In this study, we revisited whole exome sequencing datasets from non-BRCA1/2 patients, search for novel genes. Based on infinite mutation model, supposed rare non-silent variants cooccurred between TCGA-germline datasets, might play a contributing role. our analysis, not only potential pathogenic known genes, such as MRE11, CTR9 but also NCK1. According TCGA mRNA expression dataset BC, NCK1 was significantly upregulated basal-like subtypes downregulated luminal subtypes. vitro, mutants (D73H R42Q) transfected MCF7 cell lines, which attributed subtype, were much more viable invasive than wild type. On other side, results showed overall survival disease-free patients with variations be dependent genomic context. conclusion, heterogeneity exists among pedigrees could gene.