title: GNAS codon 201 mutations are uncommon in intraductal papillary neoplasms of the bile duct.
abstract: BACKGROUND
  Activating point mutations of GNAS at codon 201 have been detected in approximately two thirds of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Intraductal papillary neoplasms of the bile ducts (IPNBs) morphologically resemble pancreatic IPMNs. This study sought to assess the mutational status of GNAS at codon 201 in IPNBs.
  
  
  METHODS
  Thirty-four patients were included. DNA from microdissected IPNBs was subjected to a polymerase chain reaction and ligation method for the detection of GNAS mutations at codon 201 and of KRAS mutations at codon 12. Mutational status was compared with clinical and pathologic data.
  
  
  RESULTS
  The IPNBs had a median diameter of 3.5 cm and were located intrahepatically (n= 6), extrahepatically (n= 13), both intra- and extrahepatically (n= 4) or in the gallbladder (intracystic papillary neoplasms, n= 11). Most exhibited pancreatobiliary differentiation (n= 20), high-grade dysplasia (n= 26) and an associated adenocarcinoma (n= 20). Analysis of GNAS codon 201 identified only one mutant sample in a multifocal intestinal subtype intrahepatic IPNB with high-grade dysplasia. Six lesions harboured a KRAS codon 12 mutation.
  
  
  CONCLUSIONS
  GNAS codon 201 mutations are uncommon in IPNBs, by contrast with pancreatic IPMNs. More comprehensive molecular profiling is needed to uncover the pathways involved in IPNB development.
authors.affiliation: Departments of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Hanno
authors.initials: H
authors.lastname: Matthaei
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Marco
authors.initials: M
authors.lastname: Dal Molin
authors.forename: Marija
authors.initials: M
authors.lastname: Debeljak
authors.forename: Philipp
authors.initials: P
authors.lastname: Lingohr
authors.forename: Nora
authors.initials: N
authors.lastname: Katabi
authors.forename: David S
authors.initials: DS
authors.lastname: Klimstra
authors.forename: N Volkan
authors.initials: NV
authors.lastname: Adsay
authors.forename: James R
authors.initials: JR
authors.lastname: Eshleman
authors.forename: Richard D
authors.initials: RD
authors.lastname: Schulick
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000235:genetics* / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D017734:Bile Ducts, Extrahepatic / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D002864:Chromogranins; D003062:Codon; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D014481:United States; D018631:ras Proteins / Q000235:genetics
chemical_list: D002864:Chromogranins; D003062:Codon; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins