title: Mutational profiling reveals PIK3CA mutations in gallbladder carcinoma.
abstract: BACKGROUND
  The genetics of advanced biliary tract cancers (BTC), which encompass intra- and extra-hepatic cholangiocarcinomas as well as gallbladder carcinomas, are heterogeneous and remain to be fully defined.
  
  
  METHODS
  To better characterize mutations in established known oncogenes and tumor suppressor genes we tested a mass spectrometric based platform to interrogate common cancer associated mutations across a panel of 77 formalin fixed paraffin embedded archived BTC cases.
  
  
  RESULTS
  Mutations among three genes, KRAS, NRAS and PIK3CA were confirmed in this cohort. Activating mutations in PIK3CA were identified exclusively in GBC (4/32, 12.5%). KRAS mutations were identified in 3 (13%) intra-hepatic cholangiocarcinomas and 1 (33%) perihillar cholangiocarcinoma but were not identified in gallbladder carcinomas and extra-hepatic cholangiocarcinoma.
  
  
  CONCLUSIONS
  The presence of activating mutations in PIK3CA specifically in GBC has clinical implications in both the diagnosis of this cancer type, as well as the potential utility of targeted therapies such as PI3 kinase inhibitors.
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Deshpande
authors.forename: Afamefuna
authors.initials: A
authors.lastname: Nduaguba
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Zimmerman
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Kehoe
authors.forename: Laura E
authors.initials: LE
authors.lastname: Macconaill
authors.forename: Gregory Y
authors.initials: GY
authors.lastname: Lauwers
authors.forename: Cristina
authors.initials: C
authors.lastname: Ferrone
authors.forename: Nabeel
authors.initials: N
authors.lastname: Bardeesy
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
authors.forename: Aram F
authors.initials: AF
authors.lastname: Hezel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000378:metabolism; D011905:Genes, ras; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D054928:Validation Studies as Topic
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human