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The role of the polycomb repressive complex pathway in T and NK cell lymphoma: biological and prognostic implications

 Soo Hee Kim  ;  Woo Ick Yang  ;  Yoo Hong Min  ;  Young Hyeh Ko  ;  Sun Och Yoon 
 TUMOR BIOLOGY, Vol.37(2) : 2037-2047, 2016 
Journal Title
Issue Date
Adult ; Aged ; DNA Methylation/physiology ; Epstein-Barr Virus Infections/complications ; Female ; Histones/metabolism* ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Kaplan-Meier Estimate ; Lymphoma, Extranodal NK-T-Cell/metabolism* ; Lymphoma, Extranodal NK-T-Cell/pathology ; Lymphoma, Extranodal NK-T-Cell/virology ; Lymphoma, T-Cell/metabolism* ; Lymphoma, T-Cell/pathology ; Lymphoma, T-Cell/virology ; Male ; Middle Aged ; Polycomb Repressive Complex 1/metabolism* ; Polycomb Repressive Complex 2/metabolism* ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins c-myc/metabolism ; Tissue Array Analysis
Epstein-Barr virus ; H3K27me3 ; Lymphoma ; Polycomb repressive complex ; T and NK cell ; Trimethylation of lysine 27 of histone H3 ; c-MYC protein
Polycomb repressive complex 2 (PRC2; formed by EZH2, SUZ12, and EED protein subunits) and PRC1 (BMI1 protein) induce gene silencing through histone modification, primarily H3K27me3, and deregulation of PRC pathways leads to tumorigenesis. In the present study, activation of PRC2, H3K27me3, and BMI1 was investigated by immunohistochemistry in 175 cases of T and natural killer (NK) cell lymphoma. Activation of PRC proteins was analyzed according to c-MYC activation, Epstein-Barr virus (EBV) infection, CD30 activation, and survival. Among all T and NK cell lymphomas, high expression rates of 54.7 % for EZH2, 33.3 % for SUZ12, 85.7 % for EED, 40.5 % for H3K27me3, and 30.9 % for BMI1 were discovered. Activation of PRC2, H3K27me3, and BMI1 showed positive correlations (P < 0.05). Activation of c-MYC was associated with activation of SUZ12 and triple coactivation of all PRC2 protein subunits (EZH2(high)/SUZ12(high)/EED(high)) (P < 0.05). In EBV-positive tumors, activation of EZH2 and H3K27me3 showed greater association (P < 0.05). H3K27me3 and BMI1 showed a negative association in tumors expressing CD30 (P < 0.05). With respect to survival, BMI1 activation was independently associated with poor prognosis in T and NK cell lymphomas (P = 0.002). In conclusion, T and NK cell lymphomas were associated with activation of PRC pathway markers, for which c-MYC activation and EBV infection could be suggested as possible causes. PRC pathway markers may be potential therapeutic targets and prognostic markers in T and NK cell lymphoma.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Soo Hee(김수희)
Min, Yoo Hong(민유홍) ORCID logo https://orcid.org/0000-0001-8542-9583
Yang, Woo Ick(양우익) ORCID logo https://orcid.org/0000-0002-6084-5019
Yoon, Sun Och(윤선옥) ORCID logo https://orcid.org/0000-0002-5115-1402
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