The Mesothelioma Working Group

Malignant pleural mesothelioma (MPM) is a rare aggressive tumour for which the main risk factor is asbestos exposure. Starting in the 1990s, asbestos use was banned in several countries. However, potential sources of asbestos exposure are still widespread. Several sites where asbestos was mined or manufactured in the past and millions of square meters of asbestos cement slates still need to be cleared, creating a risk environment for people who live nearby. For example, in Italy more than 30 000 such sites are reported. The MPM mortality rate is expected to increase by 5–10% per year in most industrialized countries for the next two decades, despite asbestos abatement efforts.

The prognosis of MPM is poor, probably because of the lack of an efficient screening approach for its early detection, and the ineffectiveness of current treatments. Currently, no sensitive screening method is available to monitor people exposed to asbestos, who have a high risk of developing MPM. In recent years, epigenetic markers, such as DNA methylation and microRNA profiles, have gained popularity as possible early diagnosis and prognostic biomarkers in cancer research. The main goal of the Mesothelioma Working Group is to improve early detection and screening, in particular by evaluating risk prediction models and by identifying pre-diagnostic biomarkers.

Current projects involve the investigation of epigenetic and proteomic changes in blood and serum samples related to MPM risk and to assess the effects of asbestos exposure.

Because only a small portion of people who are exposed to asbestos develop MPM, the Working Group also focuses on the study of germline mutations that can increase susceptibility to MPM in people exposed to asbestos.

Genomic (single nucleotide polymorphism [SNP] arrays and next-generation sequencing analysis), epigenomic (DNA methylation and microRNA profiles), and biochemical (proteomics in serum) data will be integrated, with the ultimate goal of providing tools to detect early effects, to possibly enable more effective therapeutic intervention.

 

Selected publications

  1. Casalone E, Birolo G, Pardini B, Allione A, Russo A, Catalano C, et al. (2022). Serum extracellular vesicle-derived microRNAs as potential biomarkers for pleural mesothelioma in a European prospective study. Cancers (Basel). 15(1):125. https://doi.org/10.3390/cancers15010125 PMID:36612122
  2. Allione A, Viberti C, Cotellessa I, Catalano C, Casalone E, Cugliari G, et al. (2023). Blood cell DNA methylation biomarkers in preclinical malignant pleural mesothelioma: the EPIC prospective cohort. Int J Cancer. 152(4):725–37. https://doi.org/10.1002/ijc.34339 PMID:36305648
  3. Cugliari G, Catalano C, Guarrera S, Allione A, Casalone E, Russo A, et al. (2020). DNA methylation of FKBP5 as predictor of overall survival in malignant pleural mesothelioma. Cancers (Basel). 12(11):3470. https://doi.org/10.3390/cancers12113470 PMID:33233407
  4. Cugliari G, Allione A, Russo A, Catalano C, Casalone E, Guarrera S, et al. (2021). New DNA methylation signals for malignant pleural mesothelioma risk assessment. Cancers (Basel). 13(11):2636. https://doi.org/10.3390/cancers13112636 PMID:34071989
  5. Guarrera S, Viberti C, Cugliari G, Allione A, Casalone E, Betti M, et al. (2019). Peripheral blood DNA methylation as potential biomarker of malignant pleural mesothelioma in asbestos-exposed subjects. J Thorac Oncol. 14(3):527–39. https://doi.org/10.1016/j.jtho.2018.10.163 PMID:30408567
  6. Betti M, Aspesi A, Ferrante D, Sculco M, Righi L, Mirabelli D, et al. (2018). Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes. Genes Chromosomes Cancer. 57(11):573–83. https://doi.org/10.1002/gcc.22670 PMID:30338612
  7. Casalone E, Allione A, Viberti C, Pardini B, Guarrera S, Betti M, et al. (2018). DNA methylation profiling of asbestos-treated MeT5A cell line reveals novel pathways implicated in asbestos response. Arch Toxicol. 92(5):1785–95. https://doi.org/10.1007/s00204-018-2179-y PMID:29523930
  8. Kharazmi E, Chen T, Fallah M, Sundquist K, Sundquist J, Albin M, et al. (2018). Familial risk of pleural mesothelioma increased drastically in certain occupations: a nationwide prospective cohort study. Eur J Cancer. 103:1–6. https://doi.org/10.1016/j.ejca.2018.07.139 PMID:30196105
  9. Plato N, Martinsen JI, Sparén P, Hillerdal G, Weiderpass E (2016). Occupation and mesothelioma in Sweden: updated incidence in men and women in the 27 years after the asbestos ban. Epidemiol Health. 38:e2016039. https://doi.org/10.4178/epih.e2016039 PMID:27866405
  10. Tunesi S, Ferrante D, Mirabelli D, Andorno S, Betti M, Fiorito G, et al. (2015). Gene-asbestos interaction in malignant pleural mesothelioma susceptibility. Carcinogenesis. 36(10):1129–35. https://doi.org/10.1093/carcin/bgv097 PMID:26139392
  11. Matullo G, Guarrera S, Betti M, Fiorito G, Ferrante D, Voglino F, et al. (2013). Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study. PLoS One. 8(4):e61253. https://doi.org/10.1371/journal.pone.0061253 PMID:23626673
  12. Agudo A, González CA, Bleda MJ, Ramírez J, Hernández S, López F, et al. (2000). Occupation and risk of malignant pleural mesothelioma: a case-control study in Spain. Am J Ind Med. 37(2):159–68. https://doi.org/10.1002/(SICI)1097-0274(200002)37:2<159::AID-AJIM1>3.0.CO;2-0 PMID:10615096

 

Contact details/Working Group leader

Professor Giuseppe Matullo, PhD
Department of Medical Sciences
University of Turin
Via Santena 19
Turin, Italy
giuseppe.matullo@unito.it