title: Genome wide DNA copy number analysis in cholangiocarcinoma using high resolution molecular inversion probe single nucleotide polymorphism assay.
abstract: In order to study molecular similarities and differences of intrahepatic (IH-CCA) and extrahepatic (EH-CCA) cholangiocarcinoma, 24 FFPE tumor samples (13 IH-CCA, 11 EH-CCA) were analyzed for whole genome copy number variations (CNVs) using a new high-density Molecular Inversion Probe Single Nucleotide Polymorphism (MIP SNP) assay. Common in both tumor subtypes the most frequent losses were detected on chromosome 1p, 3p, 6q and 9 while gains were mostly seen in 1q, 8q as well as complete chromosome 17 and 20. Applying the statistical GISTIC (Genomic Identification of Significant Targets in Cancer) tool we identified potential novel candidate tumor suppressor- (DBC1, FHIT, PPP2R2A) and oncogenes (LYN, FGF19, GRB7, PTPN1) within these regions of chromosomal instability. Next to common aberrations in IH-CCA and EH-CCA, we additionally found significant differences in copy number variations on chromosome 3 and 14. Moreover, due to the fact that mutations in the Isocitrate dehydrogenase (IDH-1 and IDH-2) genes are more frequent in our IH-CCA than in our EH-CCA samples, we suggest that the tumor subtypes have a different molecular profile. In conclusion, new possible target genes within regions of high significant copy number aberrations were detected using a high-density Molecular Inversion Probe Single Nucleotide Polymorphism (MIP SNP) assay, which opens a future perspective of fast routine copy number and marker gene identification for gene targeted therapy.
authors.affiliation: Institute of Pathology, Charité, Universitätsmedizin Berlin, Germany; Department of Neuropathology, Charité, Universitätsmedizin Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Arnold
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Charité, Universitätsmedizin Berlin, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Bahra
authors.affiliation: Institute of Pathology, Charité, Universitätsmedizin Berlin, Germany.
authors.forename: Dido
authors.initials: D
authors.lastname: Lenze
authors.affiliation: Department of Neuropathology, Charité, Universitätsmedizin Berlin, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Bradtmöller
authors.affiliation: Department of Neuropathology, Charité, Universitätsmedizin Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Guse
authors.affiliation: Department of Neuropathology, Charité, Universitätsmedizin Berlin, Germany.
authors.forename: Claire
authors.initials: C
authors.lastname: Gehlhaar
authors.affiliation: Institute of Pathology, Charité, Universitätsmedizin Berlin, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bläker
authors.affiliation: Department of Neuropathology, Charité, Universitätsmedizin Berlin, Germany.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Heppner
authors.affiliation: Department of Neuropathology, Charité, Universitätsmedizin Berlin, Germany. Electronic address: arend.koch@charite.de.
authors.forename: Arend
authors.initials: A
authors.lastname: Koch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology; D017734:Bile Ducts, Extrahepatic / Q000378:metabolism* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D015894:Genome, Human; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D015335:Molecular Probes / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D015335:Molecular Probes; D012333:RNA, Messenger
keywords: Cholangiocarcinoma; Copy number aberrations; ERBB2; IDH; Molecular inversion probe