Identical variant TSG101 transcripts in soft tissue sarcomas and various non-neoplastic tissues

Inactivation of the TSG101 gene was recently shown to induce malignant tran sformation of NIH/3T3 fibroblasts. Abnormal TSG101 transcription profiles w ere observed in various human cancers, and large intragenic deletions of th e TSG101 gene were reported for a series of human breast cancer specimens, pointing to a potential tumor-suppressive activity of TSG101. However, subs equent more detailed studies on a large panel of breast carcinoma samples d id not confirm the tumor-associated genomic deletions. Here we analyzed the transcription patterns of the TSG101 gene in soft-tissue sarcomas and non- neoplastic human tissues. Forty-five of 71 soft tissue sarcoma samples (63% ) displayed variant transcripts; however, identical aberrant transcripts we re also detected in seven of 15 non-neoplastic control tissues. Restriction fragment length polymorphism analysis of the TSG101 gene excluded major ge nomic rearrangements in the soft tissue sarcoma samples. Northern blot anal ysis revealed a very low abundance of variant transcripts as compared with the wild-type TSG101 transcript. These data point to aberrant splicing of t he TSG101 mRNA in normal and transformed human mesenchymal tissues rather t han tumor specific alterations of the TSG101 gene. In summary, this analyse s does not support a pathogenic role for altered TSG101 expression in human soft tissue sarcomas. (C) 1998 Wiley-Liss, Inc.