title: Analysis of the TSC1 and TSC2 genes in sporadic renal cell carcinomas.
abstract: The genetic events involved in the aetiology of non-clear-cell renal cell carcinoma (RCC) and a proportion of clear cell RCC remain to be defined. Germline mutations of the TSC1 and TSC2 genes cause tuberous sclerosis (TSC), a multi-system hamartoma syndrome that is also associated with RCC. We assessed 17 sporadic clear cell RCCs with a previously identified VHL mutation, 15 clear-cell RCCs without an identified VHL mutation and 15 non-clear-cell RCCs for loss of heterozygosity (LOH) at chromosomes 9q34 and 16p13.3, the 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 region of the retained allele did not reveal any cases with a detectable intragenic second somatic mutation. Furthermore, RT-PCR analysis of TSC1 and TSC2 on total RNA from 8 clear-cell RCC cell lines confirmed expression of both TSC genes. These data indicate that biallelic inactivation of TSC1 or TSC2 is not frequent in sporadic RCC and suggests that the molecular mechanisms of renal carcinogenesis in TSC are likely to be distinct.
authors.affiliation: Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: L
authors.initials: L
authors.lastname: Parry
authors.forename: J H
authors.initials: JH
authors.lastname: Maynard
authors.forename: A
authors.initials: A
authors.lastname: Patel
authors.forename: S C
authors.initials: SC
authors.lastname: Clifford
authors.forename: C
authors.initials: C
authors.lastname: Morrissey
authors.forename: E R
authors.initials: ER
authors.lastname: Maher
authors.forename: J P
authors.initials: JP
authors.lastname: Cheadle
authors.forename: J R
authors.initials: JR
authors.lastname: Sampson
mesh_terms: D000483:Alleles; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D011506:Proteins; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins