TSG101 IS NOT MUTATED IN LUNG-CANCER BUT A SHORTENED TRANSCRIPT IS FREQUENTLY EXPRESSED IN SMALL-CELL LUNG-CANCER

TSG101 is a candidate tumor suppressor gene whose deletion in NIH3T3 c ells leads to spontaneous lung metastases in nude mice. Aberrant trans cripts of TSG101 have been identified in 47% of primary breast carcino mas, without evidence of intragenic deletions at the TSG101 locus on 1 1p15, To investigate the possible role of TSG101 in lung cancer, which often shows 11p allele loss, we performed transcript analysis and mut ational analysis of TSG101 in lung cancer cell lines. Reverse transcri ptase RT-PCR and Northern analysis detected a common TSG101 transcript , shortened because of an internal deletion, which was expressed simul taneously with the wild-type transcript in 89% of small cell lung canc er (SCLC) lines. In contrast, the wild-type transcript was expressed a lone in normal tissues, primary non-small cell lung cancer (NSCLC) spe cimens, and the majority of NSCLC cell lines. Sequence of the shortene d SCLC transcript was identical to that of the most common aberrant tr anscript identified in breast cancer, consisting of a deletion of exon s 2-4 and part of 1 and 5, Southern analysis of SCLC lines expressing the shortened transcript did not detect any intragenic deletions, Sing le strand conformational polymorphism (SSCP) analysis and direct seque ncing of TSG101 cDNAs also identified no mutations or deletions. These results suggest that TSG101 is not mutated in lung cancer but that ab errant splicing of TSG101 occurs in SCLC.