title: 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.
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.
authors.affiliation: Chair of Nutritional Toxicology, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany. scholtka@uni-potsdam.de.
authors.forename: Mandy
authors.initials: M
authors.lastname: Schneider
authors.forename: Bettina
authors.initials: B
authors.lastname: Scholtka
authors.forename: Uwe
authors.initials: U
authors.lastname: Gottschalk
authors.forename: Siegbert
authors.initials: S
authors.lastname: Faiss
authors.forename: Daniela
authors.initials: D
authors.lastname: Schatz
authors.forename: Kornelia
authors.initials: K
authors.lastname: Berghof-Jäger
authors.forename: Pablo
authors.initials: P
authors.lastname: Steinberg