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https://doi.org/10.1371/journal.pone.0111146
Title: | Molecular integrative clustering of asian gastric cell lines revealed two distinct chemosensitivity clusters | Authors: | Choong M.L. Tan S.H. Tan T.Z. Manesh S. Ngo A. Yong J.W.Y. Yang H.H. Lee M.A. |
Keywords: | 2 (2 difluoromethylbenzimidazol 1 yl) 4,6 dimorpholino 1,3,5 triazine 2 (4 hydroxyphenyl) 4 morpholinopyrido[3',2':4,5]furo[3,2 d]pyrimidine 7,8 dihydro 2 [4 (trifluoromethyl)phenyl] 5h thiopyrano[4,3 d]pyrimidin 4 ol antineoplastic agent benzyloxycarbonylleucylleucylleucinal bortezomib dactolisib dasatinib dovitinib enzyme inhibitor fluorouracil gsk 269962a luminespib midostaurin n (2,3 dihydroxypropoxy) 3,4 difluoro 2 (2 fluoro 4 iodoanilino)benzamide panobinostat phosphatidylinositol 3 kinase inhibitor pik 75 proteosome inhibitor tanespimycin unclassified drug protein kinase Article Asian cancer chemotherapy cancer survival chemosensitivity comparative genomic hybridization controlled study copy number variation drug response gastric cancer cell line gene dosage gene expression gene mutation genomics heterozygosity loss human human cell intracellular signaling mitochondrion oxidative phosphorylation stomach cancer transcription regulation Asian continental ancestry group cluster analysis drug effects genetics IC50 mutation pathology signal transduction stomach tumor tumor cell line Antineoplastic Agents Asian Continental Ancestry Group Cell Line, Tumor Cluster Analysis Humans Inhibitory Concentration 50 Mutation Protein Kinases Signal Transduction Stomach Neoplasms |
Issue Date: | 2014 | Citation: | Choong M.L., Tan S.H., Tan T.Z., Manesh S., Ngo A., Yong J.W.Y., Yang H.H., Lee M.A. (2014). Molecular integrative clustering of asian gastric cell lines revealed two distinct chemosensitivity clusters. PLoS ONE 9 (10) : e111146. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0111146 | Rights: | Attribution 4.0 International | 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. © 2014 Choong et al. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/161762 | ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0111146 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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