Frequent loss of SMAD4/DPC4 protein in colorectal cancers

Gut. 2002 Jul;51(1):56-9. doi: 10.1136/gut.51.1.56.


Background and aims: Loss of DNA sequences from chromosome 18q21 is a major genetic change in colorectal tumorigenesis. Multiple genes have been identified in this area. One of these, DPC4 (deleted in pancreatic cancer 4, also known as SMAD4), is mutated in a minor subset of colorectal carcinomas as well as in germlines of humans predisposed to colon tumours.

Patients and methods: The involvement of SMAD4 in sporadic colorectal neoplasia was evaluated by immunohistochemistry in 53 unselected cases and 27 cases displaying microsatellite instability.

Results: SMAD4 expression was absent in 20 of 53 (38%) unselected colorectal carcinomas, and reduced in another 15 (28%) cases. However, 26 of 27 cancers displaying microsatellite instability and TGF-betaIIR mutations were positive for SMAD4 immunostaining.

Conclusions: Loss of SMAD4 expression may play a more prominent role in colon cancer than anticipated based on genetic evidence, but not in mutator phenotype tumours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, Pair 18 / genetics*
  • Colorectal Neoplasms / chemistry
  • Colorectal Neoplasms / genetics*
  • DNA Mutational Analysis
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics*
  • Gene Deletion*
  • Genetic Markers
  • Humans
  • Immunohistochemistry / methods
  • Loss of Heterozygosity
  • Microsatellite Repeats
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • Smad4 Protein
  • Trans-Activators / analysis
  • Trans-Activators / genetics*


  • DNA-Binding Proteins
  • Genetic Markers
  • Receptors, Transforming Growth Factor beta
  • SMAD4 protein, human
  • Smad4 Protein
  • Trans-Activators
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II