Transforming growth factor-beta receptor type 2 mutations and microsatellite instability in sporadic colorectal adenomas and carcinomas

Am J Pathol. 1997 Jul;151(1):33-5.


Frame-shift mutations in a run of 10 adenines (A10) of the transforming growth factor-beta receptor type 2 gene (TGF-beta RII) are commonly seen in inherited and sporadic colonic cancers that exhibit microsatellite instability. A10 mutations and instability also are commonly seen in hereditary nonpolyposis colon cancer-associated adenomas. However, instability is quite rare in sporadic adenomas, and the timing of acquisition of A10 mutations with respect to the sporadic adenoma-carcinoma sequence has not been reported. We evaluated 100 sporadic colorectal cancers and 164 sporadic adenomas for microsatellite instability with a set of 10 tetranucleotide polymerase chain reaction primer sets and for A10 frame-shift mutations. A10 mutations were significantly associated with microsatellite instability in colorectal cancers, being seen in 9 of 11 cancers with 50% or greater instability and in 0 of 89 tumors with less than 50% instability (P < 0.0001). A10 mutations were not detected in any adenomas, only three of which (1.8%) exhibited significant (30% or greater) instability. We conclude that both TGF-beta RII frame-shift mutations and microsatellite instability occur at a relatively late stage of sporadic colorectal tumorigenesis. A10 frame-shift mutations appear to be restricted to sporadic colorectal cancers with extensive microsatellite instability.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoma / genetics*
  • Adenoma / pathology
  • Adult
  • Aged
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA, Satellite / analysis
  • Frameshift Mutation*
  • Humans
  • Microsatellite Repeats*
  • Middle Aged
  • Receptors, Transforming Growth Factor beta / genetics*


  • DNA, Satellite
  • Receptors, Transforming Growth Factor beta