Please use this identifier to cite or link to this item: https://doi.org/10.1002/path.2823
Title: Activated oncogenic pathways and therapeutic targets in extranodal nasal-type NK/T cell lymphoma revealed by gene expression profiling
Authors: Ng, Siok-Bian 
Selvarajan, Viknesvaran
Huang, Gaofeng
Zhou, Jianbiao 
Feldman, Andrew L
Law, Mark
Kwong, Yok-Lam
Shimizu, Norio
Kagami, Yoshitoyo
Aozasa, Katsuyuki
Salto-Tellez, Manuel
Chng, Wee-Joo 
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Pathology
NK/T-cell lymphoma
gene expression profiling
survivin
Myc
NF-kappa B
p53
paraffin-embedded tissue
NF-KAPPA-B
EPSTEIN-BARR-VIRUS
NATURAL-KILLER-CELL
T-CELL
C-MYC
PROTEASOME INHIBITOR
LEUKEMIA-LYMPHOMA
MULTIPLE-MYELOMA
IN-VITRO
MUTATIONS
Issue Date: 1-Mar-2011
Publisher: WILEY
Citation: Ng, Siok-Bian, Selvarajan, Viknesvaran, Huang, Gaofeng, Zhou, Jianbiao, Feldman, Andrew L, Law, Mark, Kwong, Yok-Lam, Shimizu, Norio, Kagami, Yoshitoyo, Aozasa, Katsuyuki, Salto-Tellez, Manuel, Chng, Wee-Joo (2011-03-01). 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
Abstract: We 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.
Source Title: JOURNAL OF PATHOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/206657
ISSN: 00223417
10969896
DOI: 10.1002/path.2823
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