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

Mandy Schneider¹  Bettina Scholtka¹  Uwe Gottschalk³  Siegbert Faiss⁴  Daniela Schatz²  Kornelia Berghof-Jäger² 

[1] Chair of Nutritional Toxicology, Institute of Nutritional Science, University of Potsdam, Arthur- Scheunert-Allee 114-116, 14558 Nuthetal, Germany; E-Mail: manschne@uni potsdam.de;BIOTECON Diagnostics GmbH, Hermannswerder Haus 17, 14473 Potsdam, Germany; E-Mails:;Maria Heimsuchung Caritas-Klinik Pankow, Breite Straße 46/47, 13187 Berlin, Germany; E-Mail:;III. Medizinische Abteilung - Gastroenterologie und Hepatologie, Asklepios Klinik Barmbek, Rubenkamp 220, 22291 Hamburg, Germany; E-Mail:

关键词: adenomas;    APC;    B-Raf;    CTNNB1;    gene mutations;    human colon;    serrated lesions;    K-Ras;    primer panel;   

DOI  :  10.3390/cancers3010091

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2010 by the authors; licensee MDPI, Basel, Switzerland.