Infrequent mutation of the tumour-suppressor gene Smad4 in early-stage colorectal cancer.
Smad4 is a candidate tumour-suppressor gene identified recently on chromosome 18q21.1. Both alleles are inactivated in nearly one-half of pancreatic carcinomas, but its role in the tumorigenesis of other tumours is still unknown. The aim of this study was to investigate the potential involvement of the Smad4 locus in early-stage colorectal cancers (stages I-III) in tumour samples from a randomised multicentre trial. Of a large collection of DNA samples, 73 with a loss of one allele of the Smad4 gene were analysed for the presence of point mutations in the remaining gene. Patients, from whom biopsies were isolated, were part of a previous randomised multicentre study of the Swiss Group for Clinical Cancer Research on the benefit of adjuvant chemotherapy (SAKK study 40/81). Mutation analysis was restricted to the highly conserved C-terminal domain (exons 8, 9, 10 and 11) of Smad4, using PCR and single-strand conformational variant analysis. Two of the 73 patients (3%) with loss of one allele of Smad4 had a point mutation in the remaining allele. These results indicate that whereas Smad4 point mutations are prevalent in pancreatic carcinoma, they are infrequent in early stages (I-III) of colorectal cancer.
Mamot
C
C
Divisin of Oncology, University Hospital Bassel, Switzerland.
Mild
G
G
Reuter
J
J
Laffer
U
U
Metzger
U
U
Terracciano
L
L
Boulay
J-L
JL
Herrmann
R
R
Rochlitz
C
C
D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation; D009367:Neoplasm Staging; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics*
D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators