TRUNCATED TSG101 TRANSCRIPTS ARE PRESENT IN PERIPHERAL-BLOOD FROM BOTH FAMILIAL BREAST-CANCER PATIENTS AND CONTROLS

TSG101 is a recently identified putative tumour suppressor gene which has been implicated in human breast cancer. To address whether germlin e disruption of TSG101 predisposes individuals to this disease, we ana lysed genomic DNA and mRNA isolated from peripheral blood from 20 fami lial breast cancer cases. No evidence of large intragenic insertions/d eletions or point mutations in TSG101 was found by Southern blot analy sis and sequence analysis of the entire coding region. However, in 11 of 20 samples,'aberrant' transcripts were detected. Sequence analysis suggested that these variants were generated by the use of different c ryptic splicing sites. Such alernative/aberrant splicing events were n ot restricted to cancer patients, but were also detected in peripheral blood of non-cancer patients and in normal tissues. (C) 1998 Elsevier Science Ltd. All rights reserved.