Tracking the Origin of Metastatic Prostate Cancer

Metastatic prostate cancer is a monoclonal disease. We previously failed to identify a common somatic denominator between primary tumor tissue and two lymph-node metastases by exome sequencing [Lindberg J, et al. Eur Urol 2013;63:702–8]. To track the seeding clone we performed copy-number alteration analysis on 34 morphologically distinct tissue areas in one prostatectomy specimen. Using break-point regions to infer phylogenetic relationships, the clone most closely related to the metastases was found in intraductal carcinoma of the prostate. Although the majority of tumor areas harbored events also found in the metastases, three carried none. This emphasizes the importance of intraprostatic tumor heterogeneity for prediction of prognosis. These findings also support recent evidence that intraductal carcinoma is a marker of aggressive disease. We identified the area in the prostate that gave rise to metastases by searching for metastatic-specific DNA alterations in multiple regions of the prostate. The metastasizing component grew within prostatic ducts, suggesting that intraductal cancer should be reported when found in needle biopsies. It is also important to be aware of tumor heterogeneity when assessing somatic changes linked to tumor aggressiveness.