Molecular pathology of prostate cancer revealed by next-generation sequencing

Abstract

This article reviews recently identified genomic mutations in prostate cancer. Advanced sequencing technologies have made it possible to obtain large amounts of data on genomes and transcriptomes of cancers. Such technologies have been used to sequence prostate cancer of different stages, from treatment-naive cancers, to advanced, castration-resistant cancers to the aggressive small cell neuroendocrine carcinomas. For each category of prostate cancer, distinct and overlapping DNA sequence alterations were discovered, including point mutations, small insertions or deletions, copy number changes and chromosomal rearrangements. There appears to be a stepwise increase in genomic alterations from low risk to high risk to advanced cancers. These novel findings have significantly increased our knowledge of the genetic basis of human prostate cancer and the molecular mechanisms responsible for disease progression and treatment resistance. Some of the lesions are potential therapeutic targets. Studies along this direction will eventually make it possible to design personalized management plans for individual patients.