BRAF, K-ras and BAT26 mutations in colorectal polyps and stool

World J Gastroenterol. 2006 Aug 28;12(32):5148-52. doi: 10.3748/wjg.v12.i32.5148.

Abstract

Aim: To assess the feasibility of using BRAF, K-ras and BAT26 genes as stool-based molecular markers for detection of colorectal adenomas and hyperplastic polyps (HPs).

Methods: We applied PCR-SSCP and direct sequencing to detect BRAF mutations of polyps and paired stool samples. Primer-mediated restriction fragment length polymorphism (RFLP) analysis and mutant-enriched PCR were used in detection of K-ras mutations of polyp tissues and paired stool samples respectively. BAT26, a microsatellite instability marker was examined by detection of small unstable alleles in a poly (A) repeat.

Results: No genetic alterations were detected in the 36 colonoscopically normal patients in either tissues or stools. BRAF, K-ras and BAT26 mutations were found in 4 (16%), 10 (40%) and 3 (12%) of 25 adenoma tissues and among them, 75%, 80% and 100% of patients were observed to contain the same mutations in their corresponding stool samples. In HPs, mutations of BRAF and K-ras were detected in the tumor DNA of 2 (11.1%) and 8 (33.3%) of 18 patients respectively, all of whom had identical alterations in their stools. Taken together, the three genetic markers detected 15 (60%) of 25 adenomas and 8 (44.4%) of 18 HPs. The sensitivity of stool detection was 80% for adenomas and 100% for HPs with an overall specificity of 92% for adenomas and 100% for HPs.

Conclusion: BRAF, K-ras and BAT26 genes have the potential to be molecular markers for colorectal adenomas and HPs, and can be used as non-invasive screening markers for colorectal polyps.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Colonic Polyps / metabolism*
  • Feces
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, ras / genetics*
  • Genetic Markers
  • Humans
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Mutation*
  • Polymorphism, Restriction Fragment Length
  • Proto-Oncogene Proteins B-raf / biosynthesis*
  • Proto-Oncogene Proteins B-raf / genetics*
  • ras Proteins / biosynthesis*

Substances

  • BAT26 microsatellite DNA
  • Biomarkers, Tumor
  • Genetic Markers
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • ras Proteins