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




Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study - Download this document for free, or read online. Document in PDF available to download.

BMC Cancer

, 5:160

First Online: 15 December 2005Received: 19 July 2005Accepted: 15 December 2005DOI: 10.1186-1471-2407-5-160

Cite this article as: Lüchtenborg, M., Weijenberg, M.P., Wark, P.A. et al. BMC Cancer 2005 5: 160. doi:10.1186-1471-2407-5-160

Abstract

BackgroundThe 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.

MethodsIn 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.

ResultsMutations 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.

ConclusionCTNNB1 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.

List of abbreviations usedAPCadenomatous polyposis coli

TP53tumour protein 53

K-rasKirsten ras

hMLH1human mut-L homologue 1

NLCSNetherlands Cohort Study on diet and cancer

NCRNetherlands Cancer Registry

PALGAPathologisch Anatomisch Landelijk Geautomatiseerd Archief

HEhaematoxylin and eosin

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-5-160 contains supplementary material, which is available to authorized users.

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Author: Margreet Lüchtenborg - Matty P Weijenberg - Petra A Wark - A Merdan Saritas - Guido MJM Roemen - Goos NP van Muijen -

Source: https://link.springer.com/







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