title: A comparison of colon and rectal somatic DNA alterations.
abstract: OBJECTIVE
  Differences in acquired mutations in colon and rectal tumors may account for differences in risk factors. In this study, we examined similarities and differences in somatic alterations in colon and rectal tumors.
  
  
  METHODS
  Cases were identified from two large population-based case-control studies of colon cancer and rectal cancer. We sequenced Exons 5 to 8 of the p53 gene and Codons 12 and 13 of the Ki-ras gene to identify tumor mutations. Microsatellite instability was determined based on BAT26 and TGFbetaRII analysis; CpG island methylator phenotype was determined based on having two or more of the following markers methylated p16, MLH1, MINT1, MINT2, and MINT31.
  
  
  RESULTS
  p53 mutations were observed in 39.7% of proximal, 51.0% of distal, and 46.6% of rectal tumors; Ki-ras mutations were observed in 36.0% of proximal, 26.9% of distal, and 30.5% of rectal tumors. Although 40.9% of proximal tumors were considered CpG island methylator phenotype positive (having two or more of five markers methylated), only 12.9% of distal and 11.9% of rectal tumors were CpG island methylator phenotype positive. Likewise, microsatellite instability was observed in 23.7% of proximal and only 3.8% of distal and 2.0% of rectal tumors. More than 50% of distal colon or rectal tumors had only one acquired mutation, whereas only 35.1% of proximal tumors had one mutation. The most common single mutation for colon and rectal tumors was p53 followed by Ki-ras mutations.
  
  
  CONCLUSIONS
  Our findings suggest that unique mutational pathways are involved in the development of most colorectal tumors. Proximal colon cancers are more likely than rectal and distal colon tumors to have microsatellite instability, CpG island methylator phenotype, and Ki-ras mutations, whereas rectal and distal colon tumors are more likely than proximal colon tumors to have a p53 mutation. Overall, rectal and distal colon tumors share similar mutational frequencies which are different from those observed in proximal colon tumors.
authors: Department of Internal Medicine, University of Utah, Salt Lake City, Utah 84108, USA. marty.slattery@hsc.utah.edu
authors: Martha L
authors: ML
authors: Slattery
authors: Karen
authors: K
authors: Curtin
authors: Roger K
authors: RK
authors: Wolff
authors: Kenneth M
authors: KM
authors: Boucher
authors: Carol
authors: C
authors: Sweeney
authors: Sandra
authors: S
authors: Edwards
authors: Bette J
authors: BJ
authors: Caan
authors: Wade
authors: W
authors: Samowitz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011509:Proteoglycans / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D012004:Rectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C516892:BAT26 microsatellite DNA; D014408:Biomarkers, Tumor; D005819:Genetic Markers; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf