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.

Research output: Journal contributionsJournal articlesResearchpeer-review

Authors

  • Mandy Schneider
  • Bettina Scholtka
  • Uwe Gottschalk
  • Siegbert Faiss
  • Daniela Schatz
  • Kornelia Berghof-Jäger
  • P. Steinberg

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.

Translated title of the contributionEntdeckung von bis zu 65 % von präkanzerogenen Läsionen des menschlichen Darms und Mastdarms durch die Mutationsanalyse von APC, K-Ras, B-Raf und CTNNB1.
Original languageEnglish
JournalCancers
Volume3
Issue number1
Pages (from-to)91-105
Number of pages15
ISSN2072-6694
DOIs
Publication statusPublished - 03.2011
Externally publishedYes

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