Analysis of the TSC1 and TSC2 genes in sporadic renal cell carcinomas (2001)

Author(s): Parry L, Maynard JH, Patel A, Clifford SC, Morrissey C, Maher ER, Cheadle JP, Sampson JR

  • : 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.

Notes: Parry, L Maynard, J H Patel, A Clifford, S C Morrissey, C Maher, E R Cheadle, J P Sampson, J R Research Support, Non-U.S. Gov't Scotland British journal of cancer Br J Cancer. 2001 Oct 19;85(8):1226-30.

  • Short Title: Analysis of the TSC1 and TSC2 genes in sporadic renal cell carcinomas
  • Date: 19-10-2001
  • Journal: British Journal of Cancer
  • Volume: 85
  • Issue: 8
  • Pages: 1226-1230
  • Publisher: Nature Publishing Group
  • Publication type: Article
  • Bibliographic status: Published

Keywords: Alleles Carcinoma, Renal Cell/ genetics Humans Kidney Neoplasms/ genetics Loss of Heterozygosity Polymorphism, Single-Stranded Conformational Proteins/ genetics Repressor Proteins/ genetics Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured Tumor Suppressor Proteins


Professor Steven Clifford
Prof of Molecular Paediatric Oncology