Transforming growth factor beta type II receptor gene mutations in adenomas from hereditary nonpolyposis colorectal cancer

Gastroenterology. 1997 Jan;112(1):33-9. doi: 10.1016/s0016-5085(97)70216-6.

Abstract

Background & aims: Germline mutations of DNA mismatch repair genes are responsible for cancer susceptibility in hereditary nonpolyposis colorectal cancer (HNPCC) kindreds. Transforming growth factor beta type II receptor (TGF-beta RII) has been found to be somatically altered in HNPCC. The aim of this study was to clarify further the role of TGF-beta RII alterations in HNPCC tumorigenesis, particularly in adenomas.

Methods: Fourteen adenoma specimens and 13 cancer specimens from 10 patients with HNPCC were screened for mutations in the short repeated sequences of the TGF-beta RII gene by polymerase chain reaction-single-strand conformation polymorphism. Mismatch repair genes, replication errors, and c-K-ras 2 were also analyzed in HNPCC tumors.

Results: Alterations of the TGF-beta RII gene at the short poly(A) repeat were found in 8 (57%) adenoma specimens and 11 (85%) cancer specimens. They were found at an earlier stage of adenomas. Two adenoma specimens showed two-hit inactivation of mismatch repair genes. Replication errors were detectable in 13 (93%) adenoma specimens. Mutations in c-K-ras 2 codon 12 were detected at a 50% frequency in adenoma specimens.

Conclusions: These data indicate a strong association between TGF-beta RII gene alterations and adenoma-carcinoma progression in HNPCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Female
  • Germ-Line Mutation / genetics
  • Humans
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Polymerase Chain Reaction
  • 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 / genetics*

Substances

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