PURPOSE: 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.
PURPOSE: 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: M L Slattery; K Curtin; K Anderson; K N Ma; S Edwards; M Leppert; J Potter; D Schaffer; W S Samowitz Journal: Cancer Res Date: 2000-12-15 Impact factor: 12.701
Authors: L H Colbert; T J Hartman; N Malila; P J Limburg; P Pietinen; J Virtamo; P R Taylor; D Albanes Journal: Cancer Epidemiol Biomarkers Prev Date: 2001-03 Impact factor: 4.254
Authors: W S Samowitz; J A Holden; K Curtin; S L Edwards; A R Walker; H A Lin; M A Robertson; M F Nichols; K M Gruenthal; B J Lynch; M F Leppert; M L Slattery Journal: Am J Pathol Date: 2001-04 Impact factor: 4.307
Authors: W S Samowitz; K Curtin; K N Ma; D Schaffer; L W Coleman; M Leppert; M L Slattery Journal: Cancer Epidemiol Biomarkers Prev Date: 2001-09 Impact factor: 4.254
Authors: M L Slattery; K Curtin; K Anderson; K N Ma; L Ballard; S Edwards; D Schaffer; J Potter; M Leppert; W S Samowitz Journal: J Natl Cancer Inst Date: 2000-11-15 Impact factor: 13.506
Authors: Jin C Kim; Young K Cho; Seon A Roh; Chang S Yu; Gyungyub Gong; Se J Jang; Seon Y Kim; Yong S Kim Journal: Cancer Sci Date: 2008-04-16 Impact factor: 6.716
Authors: Christina Dawn Williams; Jessie A Satia; Linda S Adair; June Stevens; Joseph Galanko; Temitope O Keku; Robert S Sandler Journal: Cancer Causes Control Date: 2010-03-30 Impact factor: 2.506
Authors: Wade S Samowitz; Karen Curtin; Roger K Wolff; Sheryl R Tripp; Bette J Caan; Martha L Slattery Journal: Cancer Causes Control Date: 2009-08-11 Impact factor: 2.506
Authors: Bun Kim; Soo Jung Park; Jae Hee Cheon; Tae Il Kim; Won Ho Kim; Sung Pil Hong Journal: World J Gastroenterol Date: 2014-04-21 Impact factor: 5.742
Authors: Karen Curtin; Wade S Samowitz; Roger K Wolff; Cornelia M Ulrich; Bette J Caan; John D Potter; Martha L Slattery Journal: Cancer Epidemiol Biomarkers Prev Date: 2009-12 Impact factor: 4.254
Authors: Bikash Devaraj; Aaron Lee; Betty L Cabrera; Katsumi Miyai; Linda Luo; Sonia Ramamoorthy; Temitope Keku; Robert S Sandler; Kathleen L McGuire; John M Carethers Journal: J Gastrointest Surg Date: 2010-09-16 Impact factor: 3.452