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 germline disruption of TSG101 predisposes individuals to this disease, we analysed genomic DNA and mRNA isolated from peripheral blood from 20 familial breast cancer cases. No evidence of large intragenic insertions/deletions or point mutations in TSG101 was found by Southern blot analysis 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 cryptic splicing sites. Such alternative/aberrant splicing events were not restricted to cancer patients, but were also detected in peripheral blood of non-cancer patients and in normal tissues.