A core promoter and a frequent single-nucleotide polymorphism of the mismatch repair gene hMLH1

Biochem Biophys Res Commun. 1999 Mar 24;256(3):488-94. doi: 10.1006/bbrc.1999.0368.


The hMLH1 gene encodes a protein that is involved in the DNA mismatch repair system. The coding region of the hMLH1 gene has been known to be mutated in a subset of patients with hereditary nonpolyposis colorectal cancer (HNPCC). Our current research characterized the promoter region of the hMLH1 gene and searched for mutations correlating to HNPCC. Utilizing the oligo-capping method, major transcription start sites of the hMLH1 gene were mapped at two locations. The core promoter region of about 180 bp was determined by the luciferase assay of serial deletion mutants. Although we did not find any pathogenic mutation in the hMLH1 promoter region by PCR-SSCP, we found a single-nucleotide polymorphism at position -93 nt from the adenine residue of the start codon. By PCR-RFLP analysis with Pvu II for this polymorphism, we detected LOH in four tumors from three patients. An easy detection of this polymorphism with PCR-RFLP and high incidence ( approximately 50%) of informative cases make this polymorphism a suitable marker for the detection of hMLH1 allelic losses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Base Pair Mismatch / genetics
  • Base Sequence
  • Carrier Proteins
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • DNA Mutational Analysis
  • DNA Repair / genetics*
  • DNA-Binding Proteins / metabolism
  • Deoxyribonucleotides / genetics*
  • Expressed Sequence Tags
  • Gene Frequency / genetics
  • Genotype
  • HeLa Cells
  • Humans
  • Loss of Heterozygosity / genetics
  • Mice
  • Molecular Sequence Data
  • MutL Protein Homolog 1
  • Neoplasm Proteins / genetics*
  • Nuclear Proteins
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single-Stranded Conformational
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / analysis
  • Sequence Deletion


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA-Binding Proteins
  • Deoxyribonucleotides
  • MLH1 protein, human
  • Mlh1 protein, mouse
  • Neoplasm Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • MutL Protein Homolog 1

Associated data

  • GENBANK/AB017806