DNA alterations in the tumor genome and their associations with clinical outcome in prostate cancer / 亚洲男科学杂志(英文版)

ABSTRACT

Although most prostate cancer (PCa) cases are not life-threatening, approximately 293 000 men worldwide die annually due to PCa. These lethal cases are thought to be caused by coordinated genomic alterations that accumulate over time. Recent genome-wide analyses of DNA from subjects with PCa have revealed most, if not all, genetic changes in both germline and PCa tumor genomes. In this article, I first review the major, somatically acquired genomic characteristics of various subtypes of PCa. I then recap key findings on the relationships between genomic alterations and clinical parameters, such as biochemical recurrence or clinical relapse, metastasis and cancer-specific mortality. Finally, I outline the need for, and challenges with, validation of recent findings in prospective studies for clinical utility. It is clearer now than ever before that the landscape of somatically acquired aberrations in PCa is highlighted by DNA copy number alterations (CNAs) and TMPRSS2-ERG fusion derived from complex rearrangements, numerous single nucleotide variations or mutations, tremendous heterogeneity, and continuously punctuated evolution. Genome-wide CNAs, PTEN loss, MYC gain in primary tumors, and TP53 loss/mutation and AR amplification/mutation in advanced metastatic PCa have consistently been associated with worse cancer prognosis. With this recently gained knowledge, it is now an opportune time to develop DNA-based tests that provide more accurate patient stratification for prediction of clinical outcome, which will ultimately lead to more personalized cancer care than is possible at present.