title: Immunohistochemical and DNA sequencing analysis on human mismatch repair gene MLH1 in cervical squamous cell carcinoma with LOH of this gene.
abstract: BACKGROUND
  The human MLH1 gene (hMLH1) is one of the DNA mismatch repair genes. Defects in these genes are believed to be the underlying cause of microsatellite instability (MSI). MSI has been demonstrated in many human cancers such as colon cancer and some female-specific tumors. The hMLH1 gene can be inactivated by genetic mutation or by hypermethylation of its promoter region, which often causes cessation of hMLH1 protein production. We were prompted by our previous finding of 43% of cervical cancers and their precursors with a loss of heterozygosity (LOH) of the hMLH1 gene to investigate whether it is inactivated during the carcinogenesis of cervical cancer.
  
  
  METHODS
  hMLH1 protein production was assessed by immunohistochemistry, and nucleotide sequence analysis were performed on all exons of the hMLH1 gene.
  
  
  RESULTS
  In 11 cases of invasive cervical cancer, among which 7 had LOH of the hMLH1 gene, immunohistochemistry provided no evidence for cessation of hMLH1 protein production. In addition, no mutations were found in any of the 19 hMLH1 gene exons.
  
  
  CONCLUSIONS
  The activity of hMLH1 gene might not be disturbed in the development of cervical cancer although a proportion of the cases had lost one of its hMLH1 gene copies.
authors.affiliation: Department of Genetics and Pathology, Uppsala University Hospital, Sweden. Hu.Xinrong@genpat.uu.se
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.forename: Z
authors.initials: Z
authors.lastname: Guo
authors.forename: T
authors.initials: T
authors.lastname: Pang
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: G
authors.initials: G
authors.lastname: Afink
authors.forename: J
authors.initials: J
authors.lastname: Pontén
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D020137:Base Pair Mismatch; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics*; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1