MGMT promoter methylation is a rare epigenetic change in malignant effusions

Our plain-English summary of MGMT promoter methylation is a rare epigenetic change in malignant effusions, by M. Brunetti, I. Panagopoulos, F. Micci, et al (Cytopathology, 2020).

The study

• Authors: M. Brunetti, I. Panagopoulos, F. Micci, B. Davidson
• Journal: Cytopathology
• Published: 2020;31(1):12-15
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: The aim of this study was to analyse the promoter methylation status of the gene O6-methylguanine-DNA methyltransferase (MGMT) in malignant effusions, with focus on serous carcinoma.

Methods: Fresh-frozen cell pellets from 81 effusions (42 peritoneal, 38 pleural, one pericardial), consisting of 71 carcinomas of different origin (33 ovarian, 23 breast, six lung, five uterine corpus and four cervical carcinomas) and 10 malignant mesotheliomas, were analysed for MGMT methylation using pyrosequencing analysis.

Results: MGMT methylation at all four cytosine-guanine dinucleotide sites examined was detected in only 2/81 (2%) specimens, consisting of a high-grade serous carcinoma with high frequency of methylation, and a breast carcinoma with low methylation frequency.

Conclusion: The findings in the present study suggest that MGMT methylation is a rare epigenetic change in malignant effusions of different origin.

© 2019 The Authors. Cytopathology published by John Wiley & Sons Ltd.

In plain English

This laboratory study from the Norwegian Radium Hospital in Oslo looked for a chemical change called promoter methylation in a DNA repair gene, MGMT. It used cancer cells from fluid buildups (effusions) in the body cavities of cancer patients. The researchers tested 81 effusions with a method called pyrosequencing. There were 33 from ovarian carcinoma, 23 from breast carcinoma, six from lung, five from uterine corpus and four from cervical carcinoma, plus 10 from malignant mesothelioma. Only one of the 33 ovarian carcinoma effusions showed high methylation, a high-grade serous carcinoma. Among the other 48 effusions, only one more specimen was positive, a breast carcinoma with low-level methylation. None of the mesothelioma, lung, uterine corpus or cervical effusions showed methylation. For comparison, among 12 high-grade serous carcinoma surgical (tissue) specimens, one tumour had high methylation, three had low methylation and eight were negative. The authors concluded that MGMT methylation is rare in malignant effusions and that this test does not appear to have a role in the clinical assessment of malignant serous effusions. The article does not discuss asbestos.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study of stored patient specimens (MGMT promoter methylation measured by pyrosequencing)
• Who was studied: 81 malignant effusions. These were 33 ovarian carcinoma effusions from 33 patients with advanced-stage disease diagnosed at the Norwegian Radium Hospital in 2000 to 2015, and 48 effusions from other cancers tapped in 1998 to 2008: 23 breast, six lung, five uterine corpus and four cervical carcinomas, and 10 malignant mesotheliomas of epithelioid or biphasic type. The authors also studied 12 high-grade serous carcinoma surgical specimens for comparison.
• Exposure: Not studied. The article does not address asbestos or any other exposure; it measured methylation of the MGMT gene promoter in tumour cells.
• Main results:
  • Among the 33 ovarian carcinoma effusions, only one (a peritoneal effusion with high-grade serous carcinoma) showed high methylation frequency, with values of 41% to 45% at the four sites tested.
  • Among the 48 effusions from other cancers, only one more specimen was positive: a pleural effusion from a breast carcinoma, with low-level methylation (6% to 8%).
  • None of the malignant mesothelioma effusions, or the lung, uterine corpus and cervical carcinoma effusions, showed MGMT methylation.
  • Among the 12 high-grade serous carcinoma surgical specimens, one tumour had high-frequency methylation (15.5%), three had low-frequency methylation and eight were negative.
• The authors' conclusion: The authors concluded that MGMT gene promoter methylation is rare in malignant effusions and that this test does not appear to have a role in the clinical assessment of malignant serous effusions.
• Limitations the authors state:
  • The authors stated that their ability to compare their results with earlier studies was limited. One reason is that no earlier study had analysed effusions from ovarian carcinoma patients.

Topics

Medical terms in this study, explained in our Lexicon: Carcinoma, Pericardial, Malignant Mesothelioma.

Related studies

• 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 — L.S. Kristensen, H.M. Nielsen, et al. (2011)
• Aberrant promoter methylation of WIF-1 and SFRP1, 2, 4 genes in mesothelioma — H. Kohno, V.J. Amatya, et al. (2010)
• Aberrant methylation of the CDKN2a/p16INK4a gene promoter region in preinvasive bronchial lesions: a prospective study in high-risk patients without invasive cancer — A. Lamy, R. Sesboüé, et al. (2002)
• Epigenetic down-regulation of integrin α7 increases migratory potential and confers poor prognosis in malignant pleural mesothelioma — V. Laszlo, M.A. Hoda, et al. (2015)
• Promoter methylation of DAP-kinase: association with advanced stage in non-small cell lung cancer — D.H. Kim, H.H. Nelson, et al. (2001)
• Metabolic response to pegylated arginine deiminase in mesothelioma with promoter methylation of argininosuccinate synthetase — P.W. Szlosarek, P. Luong, et al. (2013)

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