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, SunOch Yoon

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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 (EZH2high/SUZ12high/EEDhigh) (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.

Original languageEnglish
Pages (from-to)2037-2047
Number of pages11
JournalTumor Biology
Volume37
Issue number2
DOIs
Publication statusPublished - 2016 Feb 1

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Natural Killer T-Cells
Lymphoma
Epstein-Barr Virus Infections
Protein Subunits
Polycomb Repressive Complex 2
Histone Code
Gene Silencing
Human Herpesvirus 4
Neoplasms
Carcinogenesis
Proteins
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Kim, Soo Hee ; Yang, Woo Ick ; Min, Yoo Hong ; Ko, Young Hyeh ; Yoon, SunOch. / The role of the polycomb repressive complex pathway in T and NK cell lymphoma : biological and prognostic implications. In: Tumor Biology. 2016 ; Vol. 37, No. 2. pp. 2037-2047.
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abstract = "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 (EZH2high/SUZ12high/EEDhigh) (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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The role of the polycomb repressive complex pathway in T and NK cell lymphoma : biological and prognostic implications. / Kim, Soo Hee; Yang, Woo Ick; Min, Yoo Hong; Ko, Young Hyeh; Yoon, SunOch.

In: Tumor Biology, Vol. 37, No. 2, 01.02.2016, p. 2037-2047.

Research output: Contribution to journalArticle

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