Mutations of the transforming growth factor-beta type II receptor gene and genomic instability in hereditary nonpolyposis colorectal cancer

Biochem Biophys Res Commun. 1995 Nov 13;216(2):452-7. doi: 10.1006/bbrc.1995.2644.

Abstract

To determine the relation between the mutation of the TGF-beta type II receptor gene and genomic instability in the tumorigenesis of hereditary nonpolyposis colorectal cancer (HNPCC), we screened genomic DNA of 38 tumors from 25 HNPCC patients, 15 colorectal cancers from familial adenomatous polyposis patients, and 8 sporadic endometrial cancers, in two areas containing a (A)10 repeat or a (GT)3 repeat of the gene. Seventeen of the 24 (71%) genomic instability-positive HNPCC tumors carried one or two A deletions in the (A)10 repeat, while none of the 14 genomic instability-negative tumors did. These deletions inactivate the receptor through a frameshift mutation and the resultant protein truncation. No mutation was detected in the (GT)3 repeat sequence, but we found a missense mutation of codon 537 in the same area in one tumor. One A deletion was also detected in a genomic instability-positive sporadic endometrial cancer, but none in familial adenomatous polyposis tumors. No mutations were detected in the corresponding normal cells of these cases, indicating a somatic mutation. These data suggest that the TGF-beta type II receptor gene is a major target of genomic instability in HNPCC tumorigenesis.

Publication types

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

MeSH terms

  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 2*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA Primers
  • DNA, Satellite / genetics
  • Endometrial Neoplasms / genetics
  • Female
  • Humans
  • Japan
  • Liver Neoplasms / genetics
  • Liver Neoplasms / secondary
  • Lymphatic Metastasis
  • Molecular Sequence Data
  • Polymerase Chain Reaction / methods
  • Polymorphism, Single-Stranded Conformational
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics*
  • Repetitive Sequences, Nucleic Acid*
  • Stomach Neoplasms / genetics

Substances

  • DNA Primers
  • DNA, Satellite
  • Receptors, Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II

Associated data

  • GENBANK/M85079