Genetic profile of ductal adenocarcinoma of the prostate

Abstract

Despite being discovered almost 50 years ago, little is known regarding the genetic profile of ductal adenocarcinoma of the prostate (DAC). In recent years, progress has been made in the understanding of the genetics of acinar adenocarcinomas, and at least 7 genetically different subtypes have been identified. DAC is known to present at an advanced stage with a high rate of extraprostatic extension and seminal vesicle invasion, and a decreased interval to biochemical recurrence and the development of metastatic disease when compared with acinar adenocarcinoma. Our aim was to investigate the genetic profile of DAC to determine whether there is a genomic rationale for the aggressive behavior associated with this tumor type. Frozen tissue from 11 cases of DAC with paired benign tissue was analyzed. After DNA extraction, copy-number alteration analysis was performed, as well as identification of mutations and indels. We compared the fraction of the DAC genome with copy-number alteration to previous results from 74 primary acinar adenocarcinomas of the prostate. The alteration rate in DAC was comparable to that of acinar adenocarcinoma of high Gleason score. DAC harbored somatic changes seen in advanced and/or metastatic castration-resistant acinar adenocarcinoma, which likely accounts for its aggressive biological behavior.