title: Abundant copy-number loss of CYCLOPS and STOP genes in gastric adenocarcinoma.
abstract: BACKGROUND
  Gastric cancer, a leading cause of cancer death worldwide, has been little studied compared with other cancers that impose similar health burdens. Our goal is to assess genomic copy-number loss and the possible functional consequences and therapeutic implications thereof across a large series of gastric adenocarcinomas.
  
  
  METHODS
  We used high-density single-nucleotide polymorphism microarrays to determine patterns of copy-number loss and allelic imbalance in 74 gastric adenocarcinomas. We investigated whether suppressor of tumorigenesis and/or proliferation (STOP) genes are associated with genomic copy-number loss. We also analyzed the extent to which copy-number loss affects Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS (CYCLOPS) genes-genes that may be attractive targets for therapeutic inhibition when partially deleted.
  
  
  RESULTS
  The proportion of the genome subject to copy-number loss varies considerably from tumor to tumor, with a median of 5.5 %, and a mean of 12 % (range 0-58.5 %). On average, 91 STOP genes were subject to copy-number loss per tumor (median 35, range 0-452), and STOP genes tended to have lower copy-number compared with the rest of the genes. Furthermore, on average, 1.6 CYCLOPS genes per tumor were both subject to copy-number loss and downregulated, and 51.4 % of the tumors had at least one such gene.
  
  
  CONCLUSIONS
  The enrichment of STOP genes in regions of copy-number loss indicates that their deletion may contribute to gastric carcinogenesis. Furthermore, the presence of several deleted and downregulated CYCLOPS genes in some tumors suggests potential therapeutic targets in these tumors.
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.|Centre for Computational Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Ioana
authors.initials: I
authors.lastname: Cutcutache
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.|Centre for Computational Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.|Computation and Systems Biology, Singapore-MIT Alliance, Singapore, Singapore.
authors.forename: Alice Yingting
authors.initials: AY
authors.lastname: Wu
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.|Centre for Computational Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.|Centre for Computational Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: John Richard
authors.initials: JR
authors.lastname: McPherson
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.|Centre for Computational Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Zhengdeng
authors.initials: Z
authors.lastname: Lei
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.|NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore, Singapore.
authors.forename: Niantao
authors.initials: N
authors.lastname: Deng
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Shenli
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Singapore General Hospital, Singapore, Singapore.
authors.forename: Wai Keong
authors.initials: WK
authors.lastname: Wong
authors.affiliation: Department of General Surgery, Singapore General Hospital, Singapore, Singapore.|Division of Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
authors.forename: Khee Chee
authors.initials: KC
authors.lastname: Soo
authors.affiliation: Department of General Surgery, Singapore General Hospital, Singapore, Singapore.
authors.forename: Weng Hoong
authors.initials: WH
authors.lastname: Chan
authors.affiliation: Department of General Surgery, Singapore General Hospital, Singapore, Singapore.|Division of Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
authors.forename: London Lucien
authors.initials: LL
authors.lastname: Ooi
authors.affiliation: Computation and Systems Biology, Singapore-MIT Alliance, Singapore, Singapore.|Engineering Systems Division and Sloan School of Management, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Welsch
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore. gmstanp@duke-nus.edu.sg.|Computation and Systems Biology, Singapore-MIT Alliance, Singapore, Singapore. gmstanp@duke-nus.edu.sg.|Duke-NUS Genome Biology Facility, Duke-NUS Graduate Medical School, Singapore, Singapore. gmstanp@duke-nus.edu.sg.|Genome Institute of Singapore, A* STAR, Singapore, Singapore. gmstanp@duke-nus.edu.sg.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore. steve.rozen@duke-nus.edu.sg.|Centre for Computational Biology, Duke-NUS Graduate Medical School, Singapore, Singapore. steve.rozen@duke-nus.edu.sg.|Computation and Systems Biology, Singapore-MIT Alliance, Singapore, Singapore. steve.rozen@duke-nus.edu.sg.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Rozen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
keywords: DNA copy number change; Gastric cancer; Loss of heterozygosity; Tumor suppressor genes