Focal microsatellite mutations in relatives with prostatic adenocarcinoma

Instability of short tandem repeat sequences, microsatellite instability (MI), has been reported to play an important role in the tumorigenesis of various adenocarcinomas, including prostatic adenocarcinoma. Although prostate cancer is not widely recognized as a heriditary cancer, familial clustering is well known. To investigate the frequency of microsatellite instability in familial prostatic adenocarcinomas we analyzed archival tumor tissue from seven paired first degree relatives with prostatic adenocarcinoma. Twelve dinucleotide, nine trinucleotide, six tetranucleotide repeats and the CAG repeat of the androgen receptor gene were screened for MI. Solitary mutations were observed in four separate cases (28.6%) and widespread somatic alterations were not identified. No statistical correlation to pathological characteristics was determined. Our data indicate that microsatellite instability is an uncommon phenomenon in prostatic adenocarcinoma within first degree relatives. Those changes present appear to manifest as focal mutations in contrast to the more global changes seen in MI.