Please use this identifier to cite or link to this item: https://doi.org/10.1002/path.2823
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dc.titleActivated oncogenic pathways and therapeutic targets in extranodal nasal-type NK/T cell lymphoma revealed by gene expression profiling
dc.contributor.authorNg, S.-B.
dc.contributor.authorSelvarajan, V.
dc.contributor.authorHuang, G.
dc.contributor.authorZhou, J.
dc.contributor.authorFeldman, A.L.
dc.contributor.authorLaw, M.
dc.contributor.authorKwong, Y.-L.
dc.contributor.authorShimizu, N.
dc.contributor.authorKagami, Y.
dc.contributor.authorAozasa, K.
dc.contributor.authorSalto-Tellez, M.
dc.contributor.authorChng, W.-J.
dc.date.accessioned2014-11-26T07:42:30Z
dc.date.available2014-11-26T07:42:30Z
dc.date.issued2011-03
dc.identifier.citationNg, S.-B., Selvarajan, V., Huang, G., Zhou, J., Feldman, A.L., Law, M., Kwong, Y.-L., Shimizu, N., Kagami, Y., Aozasa, K., Salto-Tellez, M., Chng, W.-J. (2011-03). Activated oncogenic pathways and therapeutic targets in extranodal nasal-type NK/T cell lymphoma revealed by gene expression profiling. Journal of Pathology 223 (4) : 496-510. ScholarBank@NUS Repository. https://doi.org/10.1002/path.2823
dc.identifier.issn00223417
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/109154
dc.description.abstractWe performed comprehensive genome-wide gene expression profiling (GEP) of extranodal nasal-type natural killer/T-cell lymphoma (NKTL) using formalin-fixed, paraffin-embedded tissue (n = 9) and NK cell lines (n = 5) in comparison with normal NK cells, with the objective of understanding the oncogenic pathways involved in the pathogenesis of NKTL and to identify potential therapeutic targets. Pathway and network analysis of genes differentially expressed between NKTL and normal NK cells revealed significant enrichment for cell cycle-related genes and pathways, such as PLK1, CDK1, and Aurora-A. Furthermore, our results demonstrated a pro-proliferative and anti-apoptotic phenotype in NKTL characterized by activation of Myc and nuclear factor kappa B (NF-κB), and deregulation of p53. In corroboration with GEP findings, a significant percentage of NKTLs (n = 33) overexpressed c-Myc (45.4%), p53 (87.9%), and NF-κB p50 (67.7%) on immunohistochemistry using a tissue microarray containing 33 NKTL samples. Notably, overexpression of survivin was observed in 97% of cases. Based on our findings, we propose a model of NKTL pathogenesis where deregulation of p53 together with activation of Myc and NF-κB, possibly driven by EBV LMP-1, results in the cumulative up-regulation of survivin. Down-regulation of survivin with Terameprocol (EM-1421, a survivin inhibitor) results in reduced cell viability and increased apoptosis in tumour cells, suggesting that targeting survivin may be a potential novel therapeutic strategy in NKTL. © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1002/path.2823
dc.sourceScopus
dc.subjectgene expression profiling
dc.subjectMyc
dc.subjectNF-κB
dc.subjectNK/T-cell lymphoma
dc.subjectp53
dc.subjectparaffin-embedded tissue
dc.subjectsurvivin
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentPATHOLOGY
dc.description.doi10.1002/path.2823
dc.description.sourcetitleJournal of Pathology
dc.description.volume223
dc.description.issue4
dc.description.page496-510
dc.description.codenJPTLA
dc.identifier.isiut000287672100006
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