title: Mutation analysis and copy number changes of KRAS and BRAF genes in Taiwanese cases of biliary tract cholangiocarcinoma.
abstract: OBJECTIVE
  Cholangiocarcinoma (CC) is a fatal malignancy originating from biliary tracts and constitutes approximately 10-20% of hepatobiliary cancers. CC is characterized by a very poor prognosis. The definite molecular mechanisms leading to oncogenesis remain unclear. This study aimed to perform mutation analysis and copy number changes of KRAS and BRAF genes of CC in Taiwan.
  
  
  METHODS
  A total of 182 cases of biliary tact CC were studied for point mutation and quantitative real-time polymerase chain reaction analysis of KRAS and BRAF genes. The obtained data were analyzed with clinical and histopathological variables and survival.
  
  
  RESULTS
  KRAS point mutations were detected in intrahepatic CC (7.6%), common bile duct cancer (13.3%), and gallbladder carcinoma (3.3%). BRAF gene amplifications were demonstrated in intrahepatic CC (4.3%), common bile duct cancer (3.3%), and gallbladder cancer (5%). No association was observed between mutation patterns and histopathological features. The analyses of risk factors for overall survival in patients with CC revealed no significant association in age, tumor site, genetic mutation, or amplifications. The tumor stage was the significant prognostic factor.
  
  
  CONCLUSIONS
  Unlike other studies from American, European, or Japanese groups which showed certain levels of gene mutations in CC, our data revealed a rather low frequency of KRAS mutations and BRAF gene amplifications in CC in Taiwan. Tumor TNM stage was the only significant prognostic parameter in this analysis. It is crucial to gain more information of carcinogenesis, molecular mechanisms and therapeutic strategy in biliary tract cholangiocarcinoma.
authors.affiliation: Department of Anatomic Pathology, Far Eastern Memorial Hospital, New Taipei, Taiwan; College of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. Electronic address: pathology.taipei@gmail.com.
authors.forename: Wen-Chih
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Department of Anatomic Pathology, Far Eastern Memorial Hospital, New Taipei, Taiwan.
authors.forename: Chien-Chen
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: nivea.chan@gmail.com.
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000235:genetics*; D018281:Cholangiocarcinoma / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D013624:Taiwan
chemical_list: C117307:KRAS protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)
keywords: BRAF; KRAS; cholangiocarcinoma; mutation; survival