Cancer Research and Treatment

Original Articles

CNS cancer

Hypo-trimethylation of Histone H3 Lysine 4 and Hyper-tri/dimethylation of Histone H3 Lysine 27 as Epigenetic Markers of Poor Prognosis in Patients with Primary Central Nervous System Lymphoma: Hoon Gi Kim, Minseok S. Kim, Young Sam Lee, Eun Hee Lee, Dae Cheol Kim, Sung-Hun Lee, Young Zoon Kim; Cancer Res Treat. 2022;54(3):690-708. Published online November 17, 2021; DOI: https://doi.org/10.4143/crt.2021.1121

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Purpose
This study aimed to investigate the methylation status of major histone modification sites in primary central nervous system lymphoma (PCNSL) samples and examine their prognostic roles in patients with PCNSL.
Materials and Method
Between 2007 and 2020, 87 patients were histopathologically diagnosed with PCNSL. We performed immunohistochemical staining of the formalin-fixed paraffin-embedded samples of PCNSL for major histone modification sites, such as H3K4, H3K9, H3K27, H3K14, and H3K36. After detection of meaningful methylation sites, we examined histone modification enzymes that induce methylation or demethylation at each site using immunohistochemical staining. The meaningful immunoreactivity was validated by western blotting using fresh tissue of PCNSL.
Results
More frequent recurrences were found in hypomethylation of H3K4me3 (p=0.004) and hypermethylation of H3K27me2 (p<0.001) and H3K27me3 (p=0.002). These factors were also statistically related to short PFS and overall survival in the univariate and multivariate analyses. Next, histone modification enzymes inducing the demethylation of H3K4 (lysine-specific demethylase-1/2 and Jumonji AT-rich interactive domain [JARID] 1A-D]) and methylation of H3K27 (enhancer of zeste homolog [EZH]-1/2) were immu- nohistochemically stained. Among them, the immunoreactivity of JARID1A inversely associated with the methylation status of H3K4me3 (R²=-1.431), and immunoreactivity of EZH2 was directly associated with the methylation status of H3K27me2 (R²=0.667) and H3K27me3 (R²=0.604). These results were validated by western blotting in fresh PCNSL samples.
Conclusion
Our study suggests that hypomethylation of H3K4me3 and hypermethylation of H3K27me2 and H3K27me3 could be associated with poor outcomes in patients with PCNSL and that these relationships are modified by JARID1A and EZH2.

Citations

Citations to this article as recorded by

Updates of primary central nervous system lymphoma
Jiaying Wu, Delian Zhou, Xiaojian Zhu, Yicheng Zhang, Yi Xiao
Therapeutic Advances in Hematology.2024;[Epub] CrossRef
3-deazaneplanocin A, a histone methyltransferase inhibitor, improved the chemoresistance induced under hypoxia in melanoma cells
Mika Hosokawa, Sekai Tetsumoto, Mirano Yasui, Yusuke Kono, Ken-ichi Ogawara
Biochemical and Biophysical Research Communications.2023; 677: 26. CrossRef
Extranodal lymphoma: pathogenesis, diagnosis and treatment
Hua Yang, Yang Xun, Chao Ke, Kensuke Tateishi, Hua You
Molecular Biomedicine.2023;[Epub] CrossRef
Diagnostic and Therapeutic Perspectives Associated to Cobalamin-Dependent Metabolism and Transcobalamins’ Synthesis in Solid Cancers
Valentin Lacombe, Guy Lenaers, Geoffrey Urbanski
Nutrients.2022; 14(10): 2058. CrossRef
Primary central nervous system lymphoma: advances in its pathogenesis, molecular markers and targeted therapies
Isaias Hernández-Verdin, Andrea Morales-Martínez, Khê Hoang-Xuan, Agustí Alentorn
Current Opinion in Neurology.2022; 35(6): 779. CrossRef

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Gene Expression Profiling of Non-Small Cell Lung Cancer: Mee Sook Roh, Hyuk Chan Kwon, Jin Sook Jeong, Dae Cheol Kim, Choon Hee Son, Soo Keol Lee, Phil Jo Choi, Jae Ik Lee, Ki Nam Lee, Hyo Jin Kim, Jin Han Yoon, Tae Ho Hwang; Cancer Res Treat. 2003;35(2):154-160. Published online April 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.2.154

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PURPOSE
cDNA microarray provided a powerful alternative, with an unprecedented view scope, in monitoring gene expression levels, and led to the discovery of regulatory pathways involved in complicated biological processes. This study was performed to gain better understanding of the molecular mechanisms underlying the carcinogenesis and progression of lung cancer. MATERIALS AND METHODS: Using a cDNA microarray, representing 4, 600 cDNA clusters, we studied the expression profiles in 10 non-small cell lung cancer (NSCLC) samples and the adjacent noncancerous lung tissues form the same patients. The alterations in the levels of gene expression were confirmed by reverse-transcription PCR in 10 randomly selected genes.
RESULTS
Genes that were differently expressed in the cancerous and noncancerous tissues were identified. One hundred and nine genes (of which 68 were known) and 69 cDNAs (of which 32 were known) were up- and down-regulated in>70% of the NSCLC samples, respectively. In the cancerous tissues, the genes related to the cell cycle, metabolism, cell structure and signal transduction, were mostly up-regulated. Furthermore, we identified a few putative tumor suppressor genes that had previously been proposed by other workers. CONCLUSIONS: These results provide, not only a new molecular basis for understanding the biological properties of NSCLC, but also useful resources for the future development of diagnostic markers and therapeutic targets for NSCLC.

Citations

Citations to this article as recorded by

Expression of double‐stranded RNA‐activated protein kinase in small‐size peripheral adenocarcinoma of the lung
Mee Sook Roh, Ju Young Kwak, Su Jin Kim, Hyun Wook Lee, Hyuk Chan Kwon, Tae Ho Hwang, Phil Jo Choi, Young Seoub Hong
Pathology International.2005; 55(11): 688. CrossRef

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