FREQUENT ABNORMALITIES OF TSG101 TRANSCRIPTS IN HUMAN PROSTATE-CANCER

TSG101 has been identified as a candidate tumor suppressor gene and ab normal transcripts have been identified in a substantial fraction of b reast cancers, To determine whether TSG101 expression is commonly alte red in other tumors, a series of 15 primary and metastatic prostate ca ncers were analysed by reverse transcriptase-PCR amplification, Abnorm al transcripts with extensive deletions in the coding region were foun d in nine of these tumors, while only the normal transcript was found in control and benign prostatic hypertrophy tissues, More than one abn ormal transcript was found in four of these nine cases and distinct ab normal TSG101 transcripts were found in separate biopsies taken from o ne tumor, Importantly, the normal TSG101 transcript was undetectable i n two metastatic prostate cancers, indicating the absence of TSG101 pr otein, Sequence analysis demonstrated that there were at least sh dist inct deletions, with four of these deletions found in more than one tu mor sample, The most commonly identified deletion, from bp 153 to 1055 , was identical to a deletion reported previously in breast cancer, Th ese results demonstrate that TSG101 transcripts are frequently abnorma l in prostate cancer and suggest that loss of TSG101 protein contribut es to disease development or progression.