Epigenetic silencing status of p16INK4a and MGMT promoter regions identified qualitatively in diffuse large B cell lymphoma

Apart from genetic mutation, DNA methylation, an epigenetic event, has emerged as an important genomic disorder which silences the gene through addition of methyl group to the cytosines especially in CpG islands located in promoter region. p16, a tumor suppressor gene that inhibits cyclin-dependent...

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Main Authors:	Mohd Ridah, L Jalilah, A.Talib, Norlelawati, Hussain, Faezahtul Arbaiyah, Zainuddin, Norafiza
Format:	Article
Language:	English
Published:	Karger 2015
Subjects:	QH426 Genetics
Online Access:	http://irep.iium.edu.my/43456/ http://irep.iium.edu.my/43456/ http://irep.iium.edu.my/43456/ http://irep.iium.edu.my/43456/1/43456.pdf

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spelling	iium-434562017-08-03T03:17:18Z http://irep.iium.edu.my/43456/ Epigenetic silencing status of p16INK4a and MGMT promoter regions identified qualitatively in diffuse large B cell lymphoma Mohd Ridah, L Jalilah A.Talib, Norlelawati Hussain, Faezahtul Arbaiyah Zainuddin, Norafiza QH426 Genetics Apart from genetic mutation, DNA methylation, an epigenetic event, has emerged as an important genomic disorder which silences the gene through addition of methyl group to the cytosines especially in CpG islands located in promoter region. p16, a tumor suppressor gene that inhibits cyclin-dependent kinase, inactivates the Rb protein and blocks G1 phase in a normal cell cycle. A DNA repair gene, MGMT removes alkyl adduct to a cysteine residue within the protein, thus preventing mutagenic effects and lethal crosslinks. Methylation silencing of p16 and MGMT has been reported to associate with pathogenesis of DLBCL significantly. We aimed to screen for p16 and MGMT methylation status in DLBCL cases. Methylation status in DLBCL cases were screened using methylation specific PCR (MSP). p16 methylation was identified in 64 (73%) of 88 samples. Interestingly, MGMT methylation was detected in all cases. We found an association between p16 methylation status with patients aged >50 years old (p = 0.023). This finding is parallel with an animal study demonstrating that aging increases p16 methylation, however disconcordant to the fact, which has been revealed decades ago, thatp16 expression increases with aging. Yet to be noted, p16 methylation is not the sole determinant of p16 expression. MGMT methylation was reported to be strongly related with cancer patients who smoke, drink and are non-vegetarian. Thus, it is hypothesized that lifestyle might also trigger MGMT methylation in this study population. Conclusion: Our findings indicate that p16 and MGMT methylation were associated with DLBCL. Karger 2015 Article PeerReviewed application/pdf en http://irep.iium.edu.my/43456/1/43456.pdf Mohd Ridah, L Jalilah and A.Talib, Norlelawati and Hussain, Faezahtul Arbaiyah and Zainuddin, Norafiza (2015) Epigenetic silencing status of p16INK4a and MGMT promoter regions identified qualitatively in diffuse large B cell lymphoma. Public Health Genomics, 18 (supp.1). p. 20. ISSN 1662-4246 http://www.karger.com/Article/Abstract/381430 10.1159/000381430
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	QH426 Genetics
spellingShingle	QH426 Genetics Mohd Ridah, L Jalilah A.Talib, Norlelawati Hussain, Faezahtul Arbaiyah Zainuddin, Norafiza Epigenetic silencing status of p16INK4a and MGMT promoter regions identified qualitatively in diffuse large B cell lymphoma
description	Apart from genetic mutation, DNA methylation, an epigenetic event, has emerged as an important genomic disorder which silences the gene through addition of methyl group to the cytosines especially in CpG islands located in promoter region. p16, a tumor suppressor gene that inhibits cyclin-dependent kinase, inactivates the Rb protein and blocks G1 phase in a normal cell cycle. A DNA repair gene, MGMT removes alkyl adduct to a cysteine residue within the protein, thus preventing mutagenic effects and lethal crosslinks. Methylation silencing of p16 and MGMT has been reported to associate with pathogenesis of DLBCL significantly. We aimed to screen for p16 and MGMT methylation status in DLBCL cases. Methylation status in DLBCL cases were screened using methylation specific PCR (MSP). p16 methylation was identified in 64 (73%) of 88 samples. Interestingly, MGMT methylation was detected in all cases. We found an association between p16 methylation status with patients aged >50 years old (p = 0.023). This finding is parallel with an animal study demonstrating that aging increases p16 methylation, however disconcordant to the fact, which has been revealed decades ago, thatp16 expression increases with aging. Yet to be noted, p16 methylation is not the sole determinant of p16 expression. MGMT methylation was reported to be strongly related with cancer patients who smoke, drink and are non-vegetarian. Thus, it is hypothesized that lifestyle might also trigger MGMT methylation in this study population. Conclusion: Our findings indicate that p16 and MGMT methylation were associated with DLBCL.
format	Article
author	Mohd Ridah, L Jalilah A.Talib, Norlelawati Hussain, Faezahtul Arbaiyah Zainuddin, Norafiza
author_facet	Mohd Ridah, L Jalilah A.Talib, Norlelawati Hussain, Faezahtul Arbaiyah Zainuddin, Norafiza
author_sort	Mohd Ridah, L Jalilah
title	Epigenetic silencing status of p16INK4a and MGMT promoter regions identified qualitatively in diffuse large B cell lymphoma
title_short	Epigenetic silencing status of p16INK4a and MGMT promoter regions identified qualitatively in diffuse large B cell lymphoma
title_full	Epigenetic silencing status of p16INK4a and MGMT promoter regions identified qualitatively in diffuse large B cell lymphoma
title_fullStr	Epigenetic silencing status of p16INK4a and MGMT promoter regions identified qualitatively in diffuse large B cell lymphoma
title_full_unstemmed	Epigenetic silencing status of p16INK4a and MGMT promoter regions identified qualitatively in diffuse large B cell lymphoma
title_sort	epigenetic silencing status of p16ink4a and mgmt promoter regions identified qualitatively in diffuse large b cell lymphoma
publisher	Karger
publishDate	2015
url	http://irep.iium.edu.my/43456/ http://irep.iium.edu.my/43456/ http://irep.iium.edu.my/43456/ http://irep.iium.edu.my/43456/1/43456.pdf
first_indexed	2023-09-18T21:01:54Z
last_indexed	2023-09-18T21:01:54Z
_version_	1777410679425204224

Epigenetic silencing status of p16INK4a and MGMT promoter regions identified qualitatively in diffuse large B cell lymphoma

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