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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
Chair of Nutritional Toxicology, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany
Maria Heimsuchung Caritas-Klinik Pankow, Breite Straße 46/47, 13187 Berlin, Germany
III. Medizinische Abteilung - Gastroenterologie und Hepatologie, Asklepios Klinik Barmbek, Rübenkamp 220, 22291 Hamburg, Germany
BIOTECON Diagnostics GmbH, Hermannswerder Haus 17, 14473 Potsdam, Germany
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; in revised form: 7 December 2010 / Accepted: 20 December 2010 / Published: 29 December 2010
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
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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.
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(1):91-105.
Schneider, Mandy; Scholtka, Bettina; Gottschalk, Uwe; Faiss, Siegbert; Schatz, Daniela; Berghof-Jäger, Kornelia; Steinberg, Pablo. 2011. "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 3, no. 1: 91-105.