Identification of somatic mutations in human prostate cancer by RNA-Seq

Abstract

RNA-Seq is a recently developed tool to characterize transcriptomes using a massively parallel sequencing technique. In spite of its broad usage in gene expression profiling, RNA-Seq can also be used to discover single nucleotide variants in transcribed regions. Here we report the result of an analysis of transcriptome sequencing data of 5 human prostate cancer tissues. A total of 116 disruptive mutations (frameshift indels or nonsynonymous nucleotide substitutions) in 92 genes are revealed with high confidence. Among these genes, several candidates are of particular interest. For example, a frameshift insertion/deletion (indel) is found in the coding region of TNFSF10, which disrupts the intact open reading frame and undermines the ability of TNFSF10 to induce apoptosis, in consequence promoting abnormal tumor progression. In summary, our findings demonstrate the use of RNA-Seq in somatic mutation screening, and provide a list of candidate genes which can be used in prostate cancer diagnosis and treatment.