MGMT promoter methylation is a rare epigenetic change in malignant effusions

Abstract

The serosal cavities are a frequent site of metastasis in cancer, with adenocarcinomas of the breast, lung, female genital system and gastrointestinal tract constituting the most common sites of origin. This anatomic site is additionally the primary localisation of malignant mesothelioma (MM). 1 Tumour cells in effusions possess cancer stem cell characteristics and are chemoresistant, rendering disease at this site refractory to therapy and fatal. 1,2 Better understanding of the molecular characteristics of cells in malignant effusions is therefore critical for improving treatment options for patients with advanced disease.Aberrant promoter methylation of tumour suppressor genes is commonly observed in cancer, and is mediated through the addition of a methyl group to the carbon-5 atom of cytosine in a cytosineguanine (CpG) dinucleotide. [3][4][5] O6-Methylguanine-DNA methyltransferase, encoded by the gene MGMT, located on 10q26, is a DNA repair enzyme that protects cells against the effect of alkylating agents by eliminating the alkylation of the O6 position of guanine in the DNA. 6,7 MGMT methylation has been reported in a wide spectrum of malignancies, including glioblastoma, 8 melanoma, 9 haematological cancers 10 and carcinomas, including those of ovarian, breast, gastrointestinal and lung origin. 11 The frequency of MGMT promoter methylation in ovarian carcinoma (OC) has ranged in different series from 0% to 39% using methylation-specific polymerase chain reaction assay, variation that probably owes much to the marked differences in the tumours studied with respect to histotype. 12-20 However, none of these studies

Molecular testing on serous effusions

“…Analysis of fresh‐frozen cell pellets from 81 effusions, including 71 carcinomas (33 ovarian, 23 breast, 6 lung, 5 uterine corpus, and 4 cervical carcinomas) and 10 MM showed MGMT methylation at all 4 CpG sites in only 2 specimens, consisting of one HGSC with high frequency of methylation, and one BC with low methylation frequency. This suggests that silencing of this gene by methylation is a rare event in malignant effusions 30 …”