Significant increase of a specific variant TSG101 transcript during the progression of cervical neoplasia

The human tumour susceptibility gene TSG101 has recently been identified on chromosomal locus 11p15.1-15.2 which is frequently affected by genetic alt erations in neoplastic lesions of the uterine cervix. Aberrant transcripts of the TSG101 gene have been reported in various tumour entities, including breast, ovarian and prostate cancers, but also in several non-neoplastic t issues. We analysed TSG101 transcription by reverse transcription-polymeras e chain reaction (RT-PCR) in a total of 139 clinical samples of cervical ti ssues and in cervical carcinoma cell lines. Variant transcripts were observ ed in all cell lines, in 69 of 122 (57%) cervical dysplasia and carcinoma s amples and in five of 17 (29%) normal cervical tissues. One specific varian t TSG101 transcript (Delta 154-1054) was detected with a significantly incr eased frequency in advanced preneoplastic cervical lesions. However, the re lative abundance of variant TSG101 transcripts appeared to be generally low , as only wild-type, but no variant transcripts were detectable in Northern blot analyses of cervical carcinoma cell lines. These data point to a prog ressive loss of stringent splice control functions or to extended alternati ve splicing in advanced dysplasia and neoplasia. The relative amounts of va riant transcripts do not support a major functional role of TSG101 variants in cervical carcinogenesis. (C) 1999 Elsevier Science Ltd. All rights rese rved.