Clinicopathologic characteristics related to the high variability of coding mononucleotide repeat sequences in tumors with high-microsatellite instability

Oncol Rep. 2003 Mar-Apr;10(2):439-44.

Abstract

Frameshift mutation at coding mononucleotide repeat sequences are common in tumors with microsatellite instability (MSI-H), but the incidences are different among the target genes. We analyzed the mutational profiles of 12 known target genes containing polydeoxyadenosine repeats in their coding sequences in 39 MSI-H colorectal carcinomas and 40 MSI-H gastric carcinomas by using polymerase chain reaction and sequencing, and compared the results with the clinicopathologic characteristics. Frameshift mutations of target genes in the MSI-H colorectal and gastric carcinomas are increased according to the length of the polydeoxyadenosine repeats in the target genes. The mean mutational rates of MSI-H colorectal carcinomas and MSI-H gastric carcinomas were 2.03 and 1.95 in the 4 genes containing (A)10 repeats, 1.23 and 0.73 in the 4 genes with (A)9 repeats and 0.61 and 0.48 in the 4 genes containing (A)8 repeats, respectively (p<0.001). Among the evaluated clinicopathologic findings, intestinal type gastric carcinomas had more frameshift mutations than the diffuse type carcinomas (3.5 vs. 1.9, p=0.01). These findings suggest that mutational rates of the target genes in MSI-H tumors are diverse, and higher mutational rates are related to the length of mononucleotide repeat sequences of the target genes and histologic type of tumors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Differentiation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Female
  • Frameshift Mutation*
  • Gene Frequency
  • Humans
  • Male
  • Microsatellite Repeats / genetics*
  • Middle Aged
  • Mucins / metabolism
  • Neoplasm Proteins / genetics*
  • Neoplasm Staging
  • Open Reading Frames
  • Polymerase Chain Reaction
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*

Substances

  • DNA, Neoplasm
  • Mucins
  • Neoplasm Proteins