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Cancers 2011, 3(1), 91-105; doi:10.3390/cancers3010091

Detection of up to 65% of Precancerous Lesions of the Human Colon and Rectum by Mutation Analysis of APC, K-Ras, B-Raf and CTNNB1

1
Chair of Nutritional Toxicology, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany
2
Maria Heimsuchung Caritas-Klinik Pankow, Breite Straße 46/47, 13187 Berlin, Germany
3
III. Medizinische Abteilung - Gastroenterologie und Hepatologie, Asklepios Klinik Barmbek, Rübenkamp 220, 22291 Hamburg, Germany
4
BIOTECON Diagnostics GmbH, Hermannswerder Haus 17, 14473 Potsdam, Germany
5
Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany
These authors contributed equally to the study.
*
Authors to whom correspondence should be addressed.
Received: 24 October 2010 / Revised: 7 December 2010 / Accepted: 20 December 2010 / Published: 29 December 2010
(This article belongs to the Special Issue Prognostic and Predictive Factors in Colorectal Cancer)
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Abstract

In the present study a recently conceived 4-gene marker panel covering the Wnt and Ras-Raf-MEK-MAPK signaling pathways was used to analyze 20 colorectal serrated lesions and 41 colorectal adenoma samples and to determine the percentage of each of the above-mentioned potentially precancerous lesions carrying at least one of the four above-mentioned genes in a mutated form. CTNNB1 and B-Raf were screened by PCR-single-strand conformation polymorphism analysis, K-Ras by restriction fragment length polymorphism analysis and the APC gene mutation cluster region (codons 1243–1567) by direct DNA sequencing. APC mutations were only detected in 10% of the serrated lesions but in 34% of the adenomas. Twenty percent of the serrated lesions and 14% of the adenomas carried a mutated K-Ras. B-Raf was found to be mutated in 50% of the serrated lesions and in 22% of the adenomas. CTNNB1 was altered in 12% of the adenomas, but not in serrated lesions. By using the above gene marker panel it could be shown that 65% of the serrated lesions and 61% of the adenomas carried at least one of the four genes in a mutated form. Based on its excellent performance in detecting mutations in sporadic preneoplastic (in this study) and neoplastic lesions (in a previous study) of the human colon and rectum, this primer combination might also be suited to efficiently and non-invasively detect genetic alterations in stool DNA of patients with early colorectal cancer.
Keywords: adenomas; APC; B-Raf; CTNNB1; gene mutations; human colon; serrated lesions; K-Ras; primer panel adenomas; APC; B-Raf; CTNNB1; gene mutations; human colon; serrated lesions; K-Ras; primer panel
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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Schneider, M.; Scholtka, B.; Gottschalk, U.; Faiss, S.; Schatz, D.; Berghof-Jäger, K.; Steinberg, P. Detection of up to 65% of Precancerous Lesions of the Human Colon and Rectum by Mutation Analysis of APC, K-Ras, B-Raf and CTNNB1. Cancers 2011, 3, 91-105.

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