Analysis of TSG101 tumour susceptibility gene transcripts in cervical and endometrial cancers

Carcinoma of the uterine cervix is a common malignancy among women that has been found to show loss of heterozygosity in the chromosome 11p. Recent st udies have localized the TSG101 gene in this region, and also demonstrated a high frequency of abnormalities of this gene in human breast cancer. To d etermine the role of the TSG101 gene in the carcinogenesis of cervical and uterine carcinoma, 19 cases of cervical carcinoma and five cases of endomet rial carcinoma,as well as nearby non-cancerous tissue from the same patient s, and 16 blood samples from healthy persons as normal control were analyse d by Southern blot analysis of genomic DNA, reverse transcription of the TS G101 mRNA followed by PCR amplification and sequencing of the products. We found that abnormal transcripts of the TSG101 gene were common both in canc erous or non-cancerous tissues of the uterus and cervix and in normal perip heral mononuclear cells. There was no genomic deletion or rearrangement in spite of the presence of abnormal transcripts, and no definite relationship between the abnormal transcripts and HPV infection was found. Although the frequency of abnormal transcripts was higher in cancerous than in non-canc erous tissue, normal peripheral mononuclear cells also had abnormal transcr ipts. Given these findings, the role of the TSG101 gene as a tumour-suppres sor gene should be re-evaluated. Because some aberrant transcripts could be found at the first PCR reaction, we suggest that the aberrant transcripts might be the result of imperfect minor splicesome products.