Methylation profile landscape in mesothelioma: possible implications in early detection, disease progression, and therapeutic options

Our plain-English summary of Methylation profile landscape in mesothelioma: possible implications in early detection, disease progression, and therapeutic options, by X. Zhang, N. Tang, A.K. Rishi, et al (Methods in Molecular Biology, 2015).

The study

• Authors: X. Zhang, N. Tang, A.K. Rishi, H.I. Pass, A. Wali
• Journal: Methods in Molecular Biology
• Published: 2015;1238:235-47
• Type of article: Review
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant Pleural Mesothelioma (MPM) is an aggressive malignancy of the pleura associated with asbestos exposure. Incidence of MPM is expected to increase over the course of next decade in both Europe and the developing countries. Although significant progress has been made in terms of etiology and pathogenesis of this disease, currently available therapeutic options have not significantly improved the survival outcome of patients on standard chemotherapeutic regimens. Integrity of the cellular DNA is often altered in many cancers. Understanding of the molecular mechanisms that regulate cellular DNA alterations to facilitate cancer initiation and development has potential to allow better design of cancer cell inhibitory strategies. In this context, there is a need to explore the gamut of "omics" strategies to provide a comprehensive epigenetics profile for MPM. This chapter discusses the functional genomics and epigenetic patterns observed by various investigators studying MPM patient populations on global fronts, and attempts to present a holistic approach in combating this insidious disease. Here we provide investigators in this field with novel insights and methodologies used in other types of cancers that might have profound impact in the early detection, prognosis and potential therapeutic strategies for MPM.

In plain English

This book chapter is a narrative review, not an original study. The authors summarized published research on DNA methylation in malignant pleural mesothelioma (MPM), a cancer of the pleura (the lining around the lungs). Methylation is a chemical change that can switch genes off. The chapter describes MPM as associated with asbestos exposure. It cited a study reporting that greater asbestos exposure was significantly associated with more frequent methylation of cell cycle control genes. Drawing on other researchers' work, the authors listed genes found methylated in MPM, for example SFRP genes (80%), FHIT (78%) and CDH1 (71.4%). They described one study in which a combination of three genes (SLC6A20, SYK and APC) gave a sensitivity of 92% and a specificity of 73% in tissue samples. In another study, patients with methylation of more than one of certain genes had significantly shorter survival, although no single gene significantly influenced prognosis. The authors also reviewed laboratory and mouse studies of drugs that block methylation. They concluded that this emerging field is likely to contribute to early detection, prognosis and new combination treatments.

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: Review (book chapter) of published studies on DNA methylation and epigenetics in malignant pleural mesothelioma
• Who was studied: No study population of its own; the chapter reviewed other investigators' studies of MPM patients, tumor tissues, mesothelioma cells and mice with mesothelioma xenografts
• Exposure: The chapter's subject is DNA methylation in MPM. It describes MPM as associated with asbestos exposure and cites a study linking increased asbestos exposure to promoter methylation of cell cycle control genes. No fiber types are discussed in the text.
• Main results:
  • From cited studies: genes commonly hypermethylated in mesothelioma included SFRP (80%), FHIT (78%) and CDH1 (71.4%)
  • From a cited study of 28 loci: combining SLC6A20, SYK and APC gave a sensitivity of 92% and specificity of 73% in the tissues evaluated. The authors noted that detection in pleural fluid or blood still needed investigation.
  • From Fischer et al.: MPM patients with both RAR-beta and either DAPK or RASSF1A methylated had significantly shorter overall survival than those with one or neither, although methylation of no single gene significantly influenced prognosis
  • From a cited laboratory study: both DNMT1 silencing and decitabine treatment substantially induced death of MPM cells
  • From a cited mouse study: 5-aza-dC combined with an anti-IL-13R alpha 2 antibody suppressed tumor growth and prolonged survival of mice bearing mesothelioma xenografts
• The authors' conclusion: The authors concluded that methylation and epigenetics in mesothelioma is an emerging field likely to contribute to early detection, better prognosis and discovery of combination treatments

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Disease Progression, Pleural Mesothelioma, Pleura, Asbestos Exposure, Etiology, Prognosis.

Related studies

• The value of SHOX2 methylation test in peripheral blood samples used for the differential diagnosis of lung cancer and other lung disorders — M. Konecny, J. Markus, et al. (2016)
• DNA methylation profile of 28 potential marker loci in malignant mesothelioma — J.A. Tsou, J.S. Galler, et al. (2007)
• Distinct DNA methylation profiles in malignant mesothelioma, lung adenocarcinoma, and non-tumor lung — J.A. Tsou, L.Y. Shen, et al. (2005)
• Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection — M. Suzuki, S. Toyooka, et al. (2005)
• Mesothelioma Biomarkers: A Review Highlighting Contributions from the Early Detection Research Network — H.I. Pass, M. Alimi, et al. (2020)
• Heterogeneous Contributing Factors in MPM Disease Development and Progression: Biological Advances and Clinical Implications — B. Tolani, L.A. Acevedo, et al. (2018)

Browse more research in Methods in Molecular Biology, or return to medical research.