Methylation of MGMT in malignant pleural mesothelioma occurs in a subset of patients and is associated with the T allele of the rs16906252 MGMT promoter SNP

Lung Cancer : Journal of the International Association for the Study of Lung Cancer
Lasse Sommer KristensenLise Lotte Hansen

Abstract

Silencing of the DNA repair gene O⁶-methylguanine DNA methyltransferase (MGMT) by promoter methylation is an early event in several human cancers. MGMT removes alkyl adducts from the O⁶ position of guanine thereby preventing G>A mutations in the genome. For this reason, MGMT promoter methylation predicts a favorable outcome for glioblastoma patients treated with alkylating agents. In this study, we investigated whether MGMT becomes silenced by promoter methylation in malignant pleural mesothelioma (MPM), an aggressive cancer of the pleura associated with a poor prognosis. Ninety-five samples from patients diagnosed with MPM were studied. These samples were genotyped for the MGMT rs16906252 promoter SNP using high-resolution melting, and methylation status was analyzed using SMART-MSP and confirmed by Sanger sequencing. The SMART-MSP assay was designed to provide information on the allelic methylation status in samples heterozygous for rs16906252. MGMT immunohistochemistry was performed on samples showing no methylation, monoallelic methylation, and biallelic methylation. Thirteen of the 95 MPM samples (13.7%) were methylation positive and a strong association with the T allele of the rs16906252 SNP (P<0.001) was observed. Detec...Continue Reading

References

Apr 21, 1998·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·L L HansenT A Kruse
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Aug 3, 2002·Oncogene·Susan J Clark, John Melki
Apr 6, 2004·Nature Genetics·Catherine M SuterRobyn L Ward
Jan 11, 2005·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Jeffrey A TsouIte A Laird-Offringa
Mar 11, 2005·The New England Journal of Medicine·Monika E HegiRoger Stupp
Sep 22, 2005·Journal of the National Cancer Institute·Lanlan ShenJean-Pierre J Issa
Oct 14, 2005·The New England Journal of Medicine·Bruce W S Robinson, Richard A Lake
Dec 6, 2005·Nucleic Acids Research·Daniel J WeisenbergerPeter W Laird
Feb 16, 2007·The New England Journal of Medicine·Megan P HitchinsRobyn L Ward
Mar 14, 2007·Cancer Genetics and Cytogenetics·Paula LázcozJavier S Castresana
Apr 27, 2007·Nature Genetics·Catherine M Suter, David I K Martin
Jul 31, 2007·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Jeffrey A TsouIte A Laird-Offringa
May 17, 2008·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Lasse S Kristensen, Alexander Dobrovic
Oct 7, 2008·The International Journal of Biochemistry & Cell Biology·Alexander Dobrovic, Lasse S Kristensen
Mar 4, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Anne S TsaoHedy Lee Kindler
Sep 8, 2009·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Nicholas J HawkinsMegan P Hitchins

❮ Previous
Next ❯

Citations

Sep 21, 2011·Cancer Letters·Dimitrios Toumpanakis, Stamatios E Theocharis
Sep 18, 2014·Journal of Clinical Pharmacy and Therapeutics·J TangX-P Chen
Sep 15, 2012·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·K L McDonaldM P Hitchins
Jun 14, 2014·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Paul LochheadShuji Ogino
Sep 4, 2012·Clinical Epigenetics·Kathleen P SaavedraJuan Carlos S Roa
Jun 17, 2016·Cellular Oncology (Dordrecht)·Meixiang XuSherif Z Abdel-Rahman
Oct 11, 2013·BioTechniques·Hernán G HernándezDiego A Forero
Feb 18, 2016·Journal of Neuropathology and Experimental Neurology·Lasse S KristensenHelle Broholm
Apr 19, 2013·Current Protocols in Human Genetics·Lasse Sommer KristensenKirsten Grønbæk
Dec 7, 2019·Cytopathology : Official Journal of the British Society for Clinical Cytology·Marta BrunettiBen Davidson
Jun 9, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Joice Kuroiwa-TrzmielinaMegan P Hitchins
Sep 7, 2020·Cancer Treatment Reviews·Ilaria Fuso NeriniMaurizio D'Incalci
Jun 4, 2021·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Janah VandenhoeckKevin Lamote

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.

Cancer Epigenetics

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Cancer Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.