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BMC Cancer
Published in: BMC Cancer 1/2005

Open Access 01-12-2005 | Research article

Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

Authors: Margreet Lüchtenborg, Matty P Weijenberg, Petra A Wark, A Merdan Saritas, Guido MJM Roemen, Goos NP van Muijen, Adriaan P de Bruïne, Piet A van den Brandt, Anton FPM de Goeij

Published in: BMC Cancer | Issue 1/2005

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Abstract

Background

The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1) and Ras (K-ras) pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of these genetic alterations in relation to tumour and patient characteristics.

Methods

In a group of 656 unselected sporadic colorectal cancer patients, aberrations in the APC, K-ras, CTNNB1 genes, and expression of hMLH1 were investigated. Additionally, tumours were divided in groups based on molecular features and compared with respect to patient's age at diagnosis, sex, family history of colorectal cancer, tumour sub-localisation, Dukes' stage and differentiation.

Results

Mutations at the phosphorylation sites (codons 31, 33, 37, and 45) in the CTNNB1 gene were observed in tumours from only 5/464 patients. Tumours with truncating APC mutations and activating K-ras mutations in codons 12 and 13 occurred at similar frequencies (37% (245/656) and 36% (235/656), respectively). Seventeen percent of tumours harboured both an APC and a K-ras mutation (109/656). Nine percent of all tumours (58/656) lacked hMLH1 expression. Patients harbouring a tumour with absent hMLH1 expression were older, more often women, more often had proximal colon tumours that showed poorer differentiation when compared to patients harbouring tumours with an APC and/or K-ras mutation.

Conclusion

CTNNB1 mutations seem to be of minor importance in sporadic colorectal cancer. The main differences in tumour and patient characteristics are found between groups of patients based on mismatch repair deficiency.
Appendix
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Metadata
Title
Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study
Authors
Margreet Lüchtenborg
Matty P Weijenberg
Petra A Wark
A Merdan Saritas
Guido MJM Roemen
Goos NP van Muijen
Adriaan P de Bruïne
Piet A van den Brandt
Anton FPM de Goeij
Publication date
01-12-2005
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2005
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-5-160

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