Analysis of the TSC1 and TSC2 genes in sporadic renal cell carcinomas

The genetic events involved in the aetiology of non-clear-cell renal cell c arcinoma (RCC) and a proportion of clear cell RCC remain to be defined. Ger mline mutations of the TSC1 and TSC2 genes cause tuberous sclerosis (TSC), a multi-system hamartoma syndrome that is also associated with RCC. We asse ssed 17 sporadic clear cell RCCs with a previously identified VHL mutation, 15 clear-cell RCCs without an identified VHL mutation and 15 non-clear-cel l RCCs for loss of heterozygosity (LOH) at chromosomes 9q34 and 16p13.3, th e chromosomal locations of TSC1 and TSC2. LOH was detected in 4/9, 1/11 and 3/13 cases informative at both loci. SSCP analysis of the whole coding reg ion of the retained allele did not reveal any cases with a detectable intra genic second somatic mutation. Furthermore, RT-PCR analysis of TSC1 and TSC 2 on total RNA from 8 clear-cell RCC cell lines confirmed expression of bot h TSC genes. These data indicate that biallelic inactivation of TSC1 or TSC 2 is not frequent in sporadic RCC and suggests that the molecular mechanism s of renal carcinogenesis in TSC are likely to be distinct. (C) 2001 Cancer Research Campaign.