title: Molecular integrative clustering of Asian gastric cell lines revealed two distinct chemosensitivity clusters.
abstract: Cell lines recapitulate cancer heterogeneity without the presence of interfering tissue found in primary tumor. Their heterogeneous characteristics are reflected in their multiple genetic abnormalities and variable responsiveness to drug treatments. In order to understand the heterogeneity observed in Asian gastric cancers, we have performed array comparative genomic hybridization (aCGH) on 18 Asian gastric cell lines. Hierarchical clustering and single-sample Gene Set Enrichment Analysis were performed on the aCGH data together with public gene expression data of the same cell lines obtained from the Cancer Cell Line Encyclopedia. We found a large amount of genetic aberrations, with some cell lines having 13 fold more aberrations than others. Frequently mutated genes and cellular pathways are identified in these Asian gastric cell lines. The combined analyses of aCGH and expression data demonstrate correlation of gene copy number variations and expression profiles in human gastric cancer cells. The gastric cell lines can be grouped into 2 integrative clusters (ICs). Gastric cells in IC1 are enriched with gene associated with mitochondrial activities and oxidative phosphorylation while cells in IC2 are enriched with genes associated with cell signaling and transcription regulations. The two clusters of cell lines were shown to have distinct responsiveness towards several chemotherapeutics agents such as PI3 K and proteosome inhibitors. Our molecular integrative clustering provides insight into critical genes and pathways that may be responsible for the differences in survival in response to chemotherapy.
authors.affiliation: Experimental Therapeutics Centre, Agency for Science Technology and Research, Singapore, Singapore.
authors.forename: Meng Ling
authors.initials: ML
authors.lastname: Choong
authors.affiliation: Experimental Therapeutics Centre, Agency for Science Technology and Research, Singapore, Singapore.
authors.forename: Shan Ho
authors.initials: SH
authors.lastname: Tan
authors.affiliation: Bioinformatics Core, Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Tuan Zea
authors.initials: TZ
authors.lastname: Tan
authors.affiliation: Experimental Therapeutics Centre, Agency for Science Technology and Research, Singapore, Singapore.
authors.forename: Sravanthy
authors.initials: S
authors.lastname: Manesh
authors.affiliation: Experimental Therapeutics Centre, Agency for Science Technology and Research, Singapore, Singapore.
authors.forename: Anna
authors.initials: A
authors.lastname: Ngo
authors.affiliation: Experimental Therapeutics Centre, Agency for Science Technology and Research, Singapore, Singapore.
authors.forename: Jacklyn W Y
authors.initials: JW
authors.lastname: Yong
authors.affiliation: Bioinformatics Core, Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Henry He
authors.initials: HH
authors.lastname: Yang
authors.affiliation: Experimental Therapeutics Centre, Agency for Science Technology and Research, Singapore, Singapore.
authors.forename: May Ann
authors.initials: MA
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D044466:Asian People; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D006801:Humans; D020128:Inhibitory Concentration 50; D009154:Mutation / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D011494:Protein Kinases