Epigenetic methylation status of P16, MGMT and SPOCK2 in diffuse Large B cell lymphoma
Introduction: Epigenetic methylation has been implicated in the pathogenesis of diffuse large B cell lymphoma (DLBCL). This study investigated the methylation status of p16, MGMT and SPOCK2. Aberrantly methylated p16 and MGMT have been linked to DLBCL, but not SPOCK2. p16 inhibits cyclin-dependent k...
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iium-543782017-01-20T04:24:58Z http://irep.iium.edu.my/54378/ Epigenetic methylation status of P16, MGMT and SPOCK2 in diffuse Large B cell lymphoma Mohd. Ridah, Lailatul Jalilah Ismail, Aziah A. Talib, Norlelawati Muhammad, Siti Aesah @ Naznin Hussain, Faezahtul Arbaiyah Zainuddin, Norafiza RC0254 Neoplasms. Tumors. Oncology (including Cancer) Introduction: Epigenetic methylation has been implicated in the pathogenesis of diffuse large B cell lymphoma (DLBCL). This study investigated the methylation status of p16, MGMT and SPOCK2. Aberrantly methylated p16 and MGMT have been linked to DLBCL, but not SPOCK2. p16 inhibits cyclin-dependent kinase, which results in retinoblastoma phosphorylation and blockage of cell cycle at G1 phase. MGMT removes alkyl adduct at O6-guanine, thus preventing lethal cross-links. SPOCK2, an extracellular chondroitin and heparin sulfate proteoglycans, abolishes the inhibition of membrane-type 1-matrix metalloproteinase which might enhance the angiogenesis. The absence of SPOCK2 methylation was therefore hypothesized in the majority of cases in this study. Methods: Extracted DNA from 88 formalin-fixed paraffin-embedded (FFPE) tissues of DLBCL were subjected to bisulfite conversion followed by methylation-specific PCR (MSP) analysis for p16, MGMT and SPOCK2 methylation. p16 methylation was also quantified in 16 samples through pyrosequencing assay. Results: p16 methylation was observed in 65/88 (74%) samples by MSP. Pyrosequencing detected p16 methylation in all 16 samples ranging from 18% to 81%. MGMT methylation was detected in all 88 (100%) cases. Methylated SPOCK2 was found in 83 (94.3%) samples. There was a significant association between p16 methylation status with patients above 50 years of age (p= 0.04). Conclusions: These preliminary discoveries may serve as a good platform in order to gain a comprehensive overview on the epigenetics contribution in the pathogenesis of DLBCL. Pyrosequencing is a robust tool in detecting and quantifying methylation. IIUM 2016-12 Conference or Workshop Item PeerReviewed application/pdf en http://irep.iium.edu.my/54378/1/MRS2016-ABSTRACT-BOOK-5.pdf application/pdf en http://irep.iium.edu.my/54378/7/54378_epigenetic%20methylation.pdf Mohd. Ridah, Lailatul Jalilah and Ismail, Aziah and A. Talib, Norlelawati and Muhammad, Siti Aesah @ Naznin and Hussain, Faezahtul Arbaiyah and Zainuddin, Norafiza (2016) Epigenetic methylation status of P16, MGMT and SPOCK2 in diffuse Large B cell lymphoma. In: Medical Research Symposium & Pacific Partnership in conjunction with Kuantan Research Day 2016, 3rd-5th August 2016, Kuantan, Pahang. http://iiumedic.net/imjm/v1/ |
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RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
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RC0254 Neoplasms. Tumors. Oncology (including Cancer) Mohd. Ridah, Lailatul Jalilah Ismail, Aziah A. Talib, Norlelawati Muhammad, Siti Aesah @ Naznin Hussain, Faezahtul Arbaiyah Zainuddin, Norafiza Epigenetic methylation status of P16, MGMT and SPOCK2 in diffuse Large B cell lymphoma |
description |
Introduction: Epigenetic methylation has been implicated in the pathogenesis of diffuse large B cell lymphoma (DLBCL). This study investigated the methylation status of p16, MGMT and SPOCK2. Aberrantly methylated p16 and MGMT have been linked to DLBCL, but not SPOCK2. p16 inhibits cyclin-dependent kinase, which results in retinoblastoma phosphorylation and blockage of cell cycle at G1 phase. MGMT removes alkyl adduct at O6-guanine, thus preventing lethal cross-links. SPOCK2, an extracellular chondroitin and heparin sulfate proteoglycans, abolishes the inhibition of membrane-type 1-matrix metalloproteinase which might enhance the angiogenesis. The absence of SPOCK2 methylation was therefore hypothesized in the majority of cases in this study. Methods: Extracted DNA from 88 formalin-fixed paraffin-embedded (FFPE) tissues of DLBCL were subjected to bisulfite conversion followed by methylation-specific PCR (MSP) analysis for p16, MGMT and SPOCK2 methylation. p16 methylation was also quantified in 16 samples through pyrosequencing assay. Results: p16 methylation was observed in 65/88 (74%) samples by MSP. Pyrosequencing detected p16 methylation in all 16 samples ranging from 18% to 81%. MGMT methylation was detected in all 88 (100%) cases. Methylated SPOCK2 was found in 83 (94.3%) samples. There was a significant association between p16 methylation status with patients above 50 years of age (p= 0.04). Conclusions: These preliminary discoveries may serve as a good platform in order to gain a comprehensive overview on the epigenetics contribution in the pathogenesis of DLBCL. Pyrosequencing is a robust tool in detecting and quantifying methylation. |
format |
Conference or Workshop Item |
author |
Mohd. Ridah, Lailatul Jalilah Ismail, Aziah A. Talib, Norlelawati Muhammad, Siti Aesah @ Naznin Hussain, Faezahtul Arbaiyah Zainuddin, Norafiza |
author_facet |
Mohd. Ridah, Lailatul Jalilah Ismail, Aziah A. Talib, Norlelawati Muhammad, Siti Aesah @ Naznin Hussain, Faezahtul Arbaiyah Zainuddin, Norafiza |
author_sort |
Mohd. Ridah, Lailatul Jalilah |
title |
Epigenetic methylation status of P16, MGMT and SPOCK2 in diffuse Large B cell lymphoma |
title_short |
Epigenetic methylation status of P16, MGMT and SPOCK2 in diffuse Large B cell lymphoma |
title_full |
Epigenetic methylation status of P16, MGMT and SPOCK2 in diffuse Large B cell lymphoma |
title_fullStr |
Epigenetic methylation status of P16, MGMT and SPOCK2 in diffuse Large B cell lymphoma |
title_full_unstemmed |
Epigenetic methylation status of P16, MGMT and SPOCK2 in diffuse Large B cell lymphoma |
title_sort |
epigenetic methylation status of p16, mgmt and spock2 in diffuse large b cell lymphoma |
publisher |
IIUM |
publishDate |
2016 |
url |
http://irep.iium.edu.my/54378/ http://irep.iium.edu.my/54378/ http://irep.iium.edu.my/54378/1/MRS2016-ABSTRACT-BOOK-5.pdf http://irep.iium.edu.my/54378/7/54378_epigenetic%20methylation.pdf |
first_indexed |
2023-09-18T21:16:56Z |
last_indexed |
2023-09-18T21:16:56Z |
_version_ |
1777411624829714432 |