论文部分内容阅读
Genome-Wide Association Studies (GWAS) and whole-genome re-sequencing studies have identified thousands of germline risk variants and somatic mutations in cancer.However, efforts to interpret these data have mainly focused on protein coding genes, despite the fact that majority of these genetic alterations locate outside of coding gene exons.A recent curation of over seven thousand RNA-Seq data characterized more than 58000 expressed long noncoding RNAs (lncRNAs) in human genome, twice as large as the number of protein coding genes.We integrated lncRNA gene expression, epigenetic and genetic alteration data to nominate potential driver lncRNAs in prostate cancer.We identified 55 candidate lncRNAs and experimental validation shows that they can be regulated by risk SNPs and somatic mutations through both cis and trans actions.The function of two of these lncRNAs in prostate cancer development and progression has been characterized.Our data suggests that genetic variations in noncoding regions function largely through regulating lncRNA expression and these lncRNAs may serve as new biomarkers for personalized medicine.