title: Integrated genomic, transcriptomic, and RNA-interference analysis of genes in somatic copy number gains in pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  This study used an integrated analysis of copy number, gene expression, and RNA interference screens for identification of putative driver genes harbored in somatic copy number gains in pancreatic ductal adenocarcinoma (PDAC).
  
  
  METHODS
  Somatic copy number gain data on 60 PDAC genomes were extracted from public data sets to identify genomic loci that are recurrently gained. Array-based data from a panel of 29 human PDAC cell lines were used to quantify associations between copy number and gene expression for the set of genes found in somatic copy number gains. The most highly correlated genes were assessed in a compendium of pooled short hairpin RNA screens on 27 of the same human PDAC cell lines.
  
  
  RESULTS
  A catalog of 710 protein-coding and 46 RNA genes mapping to 20 recurrently gained genomic loci were identified. The gene set was further refined through stringent integration of copy number, gene expression, and RNA interference screening data to uncover 34 candidate driver genes.
  
  
  CONCLUSIONS
  Among the candidate genes from the integrative analysis, ECT2 was found to have significantly higher essentiality in specific PDAC cell lines with genomic gains at the 3q26.3 locus, which harbors this gene, suggesting that ECT2 may play an oncogenic role in the PDAC neoplastic process.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nardin
authors.initials: N
authors.lastname: Samuel
authors.forename: Azin
authors.initials: A
authors.lastname: Sayad
authors.forename: Gavin
authors.initials: G
authors.lastname: Wilson
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lemire
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Brown
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Muthuswamy
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: Jason
authors.initials: J
authors.lastname: Moffat
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D056915:DNA Copy Number Variations; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000235:genetics; D023281:Genomics; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011518:Proto-Oncogene Proteins / Q000235:genetics; D034622:RNA Interference; D059467:Transcriptome
chemical_list: C489850:ECT2 protein, human; D011518:Proto-Oncogene Proteins