title: Array comparative genomic hybridization identifies novel potential therapeutic targets in cholangiocarcinoma.
abstract: BACKGROUND
  Cholangiocarcinoma (CC) is a rare tumour with a dismal prognosis. As conventional medical management offers minimal survival benefit, surgery currently represents the only chance of cure. We evaluated DNA copy number (CN) alterations in CC to identify novel therapeutic targets.
  
  
  METHODS
  DNA was extracted from 32 CC samples. Bacterial artificial chromosome (BAC) array comparative genomic hybridization was performed using microarray slides containing 3400 BAC clones covering the whole human genome at distances of 1 Mb. Data were analysed within the R statistical environment.
  
  
  RESULTS
  DNA CN gains (89 regions) occurred more frequently than DNA CN losses (55 regions). Six regions of gain were identified in all cases on chromosomes 16, 17, 19 and 22. Twenty regions were frequently gained on chromosomes 1, 5, 7, 9, 11, 12, 16, 17, 19, 20 and 21. The BAC clones covering ERBB2, MEK2 and PDGFB genes were gained in all cases. Regions covering MTOR, VEGFR 3, PDGFA, RAF1, VEGFA and EGFR genes were frequently gained.
  
  
  CONCLUSIONS
  We identified CN gains in the region of 11 useful molecular targets. Findings of variable gains in some regions in this and other studies support the argument for molecular stratification before treatment for CC so that treatment can be tailored to the individual patient.
authors.affiliation: Department of Hepatopancreaticobiliary Surgery, Imperial College London, London, UK. siobhan.mckay08@imperial.ac.uk
authors.forename: Siobhan C
authors.initials: SC
authors.lastname: McKay
authors.forename: Kristian
authors.initials: K
authors.lastname: Unger
authors.forename: Stephanos
authors.initials: S
authors.lastname: Pericleous
authors.forename: Gordon
authors.initials: G
authors.lastname: Stamp
authors.forename: Gerry
authors.initials: G
authors.lastname: Thomas
authors.forename: Robert R
authors.initials: RR
authors.lastname: Hutchins
authors.forename: Duncan R C
authors.initials: DR
authors.lastname: Spalding
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D001653:Bile Ducts, Intrahepatic / Q000737:chemistry / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D018281:Cholangiocarcinoma / Q000737:chemistry / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D022202:Chromosomes, Artificial, Bacterial; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D020411:Oligonucleotide Array Sequence Analysis; D018579:Patient Selection; D057285:Precision Medicine; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human