title: [Promoter hypermethylation status of the mismatch repair gene hMLH1 in patients with sporadic renal cell carcinoma].
abstract: OBJECTIVE
  Epigenetic inactivation is a gene function abnormality that produces no changes in the DNA sequence, with the most frequent epigenetic alteration being hypermethylation of CpG islands in the promoter regions of the genes. Based on recent indications of a potential relationship between mismatch repair genes and renal cell carcinoma (RCC), we were interested in investigating the existence of promoter hypermethylation of the hMLH1 gene in tumor DNA samples from patients with sporadic RCC.
  
  
  METHODS
  Sixty-five tumor tissue specimens were collected consecutively. The DNA was first obtained and purified, then digested with the restriction enzymes Hpa II and Msp I, followed by polimerase chain reaction amplification of 3 promoter regions of the hMLH1 gene, agarose gel electrophoresis, and densitometric analysis of the images of the amplified bands.
  
  
  RESULTS
  Mean patient age was 63.7 years. The most frequent cell type was clear cell carcinoma (67.7%). 73.9% of tumors were diagnosed in stages below pT2, 9.3% had gland involvement and 20%, distant metastasis. No somatic hypermethylation was detected in the promoter region of the hMLH1 gene in any of the patients studied.
  
  
  CONCLUSIONS
  Our data indicate that promoter hypermethylation of the hMLH1 gene is not implicated in the pathogenesis of sporadic RCC, and therefore the existence of another type of mutation, microsatellite instability and/or loss of heterozygosity should be examined to determine the possible role of this gene in sporadic RCC.
authors.affiliation: Servicio de Urología, Complejo Hospitalario y Universitario de Albacete, Albacete, Spain. asalinas@pulso.com
authors.forename: Antonio S
authors.initials: AS
authors.lastname: Salinas-Sánchez
authors.forename: Antonio
authors.initials: A
authors.lastname: Rubio-del-Campo
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Sánchez
authors.forename: José M
authors.initials: JM
authors.lastname: Giménez-Bachs
authors.forename: María J
authors.initials: MJ
authors.lastname: Donate-Moreno
authors.forename: Dolores C
authors.initials: DC
authors.lastname: García-Olmo
authors.forename: Julio
authors.initials: J
authors.lastname: Escribano-Martínez
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D019175:DNA Methylation; D004260:DNA Repair; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1