title: Molecular profiling of cholangiocarcinoma shows potential for targeted therapy treatment decisions.
abstract: Cholangiocarcinoma is a highly lethal cancer of the biliary tract. The intrahepatic subtype of cholangiocarcinoma is increasing in incidence globally. Despite technologic advancements over the past decade, little is known about the somatic changes that occur in these tumors. The goal of this study was to determine the frequency of common oncogenes in resected cholangiocarcinoma specimens that could provide potential therapeutic targets for patients diagnosed with cholangiocarcinoma. Formalin-fixed, paraffin-embedded tissue blocks from 94 resected cholangiocarcinomas were used to extract DNA from areas comprising more than 20% tumor. Specimens were evaluated using the Sequenom MassARRAY OncoCarta Mutation Profiler Panel (San Diego, CA). This matrix-assisted laser desorption/ionization-time of flight mass spectrometry single genotyping panel evaluates 19 oncogenes for 238 somatic mutations. Twenty-five mutations were identified in 23 of the 94 cholangiocarcinomas within the following oncogenes: KRAS (n = 12), PIK3CA (n = 5), MET (n = 4), EGFR (n = 1), BRAF (n = 2), and NRAS (n = 1). Mutations were identified in 7 (26%) of 27 extrahepatic cholangiocarcinomas and 16 (24%) of 67 intrahepatic cholangiocarcinomas. When combined with IDH1/2 testing, 40 (43%) of the 94 cholangiocarcinomas had a detectable mutation. MassARRAY technology can be used to detect mutations in a wide variety of oncogenes using paraffin-embedded tissue. Clinical testing for somatic mutations may drive personalized therapy selection for cholangiocarcinomas in the future. The variety of mutations detected suggests that a multiplexed mutation detection approach may be necessary for managing patients with biliary tract malignancy.
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors: Jesse S
authors: JS
authors: Voss
authors: Leonard M
authors: LM
authors: Holtegaard
authors: Sarah E
authors: SE
authors: Kerr
authors: Emily G Barr
authors: EG
authors: Fritcher
authors: Lewis R
authors: LR
authors: Roberts
authors: Gregory J
authors: GJ
authors: Gores
authors: Jun
authors: J
authors: Zhang
authors: W Edward
authors: WE
authors: Highsmith
authors: Kevin C
authors: KC
authors: Halling
authors: Benjamin R
authors: BR
authors: Kipp
mesh_terms: D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000235:genetics; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human