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...

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Bibliographic Details
Published in:British journal of cancer 2003-02, Vol.88 (3), p.420-423
Main Authors: MAMOT, C, MILD, G, REUTER, J, LAFFER, U, METZGER, U, TERRACCIANO, L, BOULAY, J-L, HERRMANN, R, ROCHLITZ, C
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cancer research
Chemotherapy
Chromosomes
Clinical Trials as Topic
Colorectal cancer
Colorectal Neoplasms - genetics
DNA-Binding Proteins - genetics
Gastroenterology. Liver. Pancreas. Abdomen
Gene Dosage
Genes
Humans
Kinases
Loss of Heterozygosity
Medical research
Medical sciences
Molecular and Cellular Pathology
Mutation
Neoplasm Staging
Oncology
Pancreatic cancer
Signal transduction
Smad4 Protein
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Trans-Activators - genetics
Tumors
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Summary: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.
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6600733