title: KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients.
abstract: OBJECTIVE
  To investigate gene mutations and DNA mismatch repair (MMR) protein abnormality in Chinese colorectal carcinoma (CRC) patients and their correlations with clinicopathologic features.
  
  
  METHODS
  Clinical and pathological information for 535 patients including 538 tumors was reviewed and recorded. Mutation analyses for exon 2 of KRAS gene and exon 15 of BRAF gene were performed by Sanger sequencing except that in 9 tumors amplification refractory mutation system PCR was used. Expression of MMR proteins including MHL1, MSH2, MSH6 and PMS2 was evaluated by immunohistochemistry. Correlations of KRAS and BRAF mutation status and the expression status of MMR proteins with age, gender, cancer stage, location, and histology were analyzed. Correlations between KRAS or BRAF mutations and MMR protein expression were also explored.
  
  
  RESULTS
  The overall frequencies of KRAS and BRAF mutations were 37.9% and 4.4%, respectively. KRAS mutations were more common in patients ≥ 50 years old (39.8% vs 22% in patients < 50 years old, P < 0.05). The frequencies of BRAF mutants were higher in tumors from females (6.6% vs males 2.8%, P < 0.05), located in the right colon (9.6% vs 2.1% in the left colon, 1.8% in the rectum, P < 0.01), with mucinous differentiation (9.8% vs 2.8% without mucinous differentiation, P < 0.01), or being poorly differentiated (9.5% vs 3.4% well/moderately differentiated, P < 0.05). MMR deficiency was strongly associated with proximal location (20.5% in the right colon vs 9.2% in the left colon and 5.1% in the rectum, P < 0.001), early cancer stage (15.0% in stages I-II vs 7.7% in stages III-IV, P < 0.05), and mucinous differentiation (20.2% vs 9.2% without mucin, P < 0.01). A higher frequency of MLH1/PMS2 loss was found in females (9.2% vs 4.4% in males, P < 0.05), and MSH2/MSH6 loss tended to be seen in younger (<50 years old) patients (12.0% vs 4.0% ≥ 50 years old, P < 0.05). MMR deficient tumors were less likely to have KRAS mutations (18.8% vs 41.7% in MMR proficient tumors, P < 0.05) and tumors with abnormal MLH1/PMS2 tended to harbor BRAF mutations (15.4% vs 4.2% in MMR proficient tumors, P < 0.05).
  
  
  CONCLUSIONS
  The frequency of sporadic CRCs having BRAF mutation, MLH1 deficiency and MSI in Chinese population may be lower than that in the Western population.
authors: Ju-Xiang Ye, Yan Liu, Yun Qin, Hao-Hao Zhong, Xue-Ying Shi, Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing 100191, China.
authors: Ju-Xiang
authors: JX
authors: Ye
authors: Ju-Xiang Ye, Yan Liu, Yun Qin, Hao-Hao Zhong, Xue-Ying Shi, Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing 100191, China.
authors: Yan
authors: Y
authors: Liu
authors: Ju-Xiang Ye, Yan Liu, Yun Qin, Hao-Hao Zhong, Xue-Ying Shi, Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing 100191, China.
authors: Yun
authors: Y
authors: Qin
authors: Ju-Xiang Ye, Yan Liu, Yun Qin, Hao-Hao Zhong, Xue-Ying Shi, Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing 100191, China.
authors: Hao-Hao
authors: HH
authors: Zhong
authors: Ju-Xiang Ye, Yan Liu, Yun Qin, Hao-Hao Zhong, Xue-Ying Shi, Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing 100191, China.
authors: Wei-Ning
authors: WN
authors: Yi
authors: Ju-Xiang Ye, Yan Liu, Yun Qin, Hao-Hao Zhong, Xue-Ying Shi, Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing 100191, China.
authors: Xue-Ying
authors: XY
authors: Shi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000230:Adenocarcinoma / Q000208:ethnology / Q000235:genetics* / Q000556:secondary; D000368:Aged; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D002454:Cell Differentiation; D002681:China / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D008969:Molecular Sequence Data; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D012307:Risk Factors; D018631:ras Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: BRAF; Colorectal carcinoma; DNA mismatch repair; KRAS; MLH1; MSH2; MSH6; PMS2