5-hydroxymethylcytosine but not MTAP methylation status can stratify malignant pleural mesothelioma based on the lineage of origin
Abstract Background Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, mainly associated with work or environmental exposure to asbestos. MPM’s molecular profile is largerly unexplored and effective therapies are still lacking. MPM rarely harbours those somatic genetic...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
PAGEPress Publications
2018-08-01
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| Series: | Multidisciplinary Respiratory Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40248-018-0137-4 |
| _version_ | 1797283336105754624 |
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| author | Matteo Bosio Elena Salvaterra Francesca Datturi Patrizia Morbini Michele Zorzetto Simona Inghilleri Stefano Tomaselli Patrizia Mangiarotti Federica Meloni Isa Cerveri Giulia Maria Stella |
| author_facet | Matteo Bosio Elena Salvaterra Francesca Datturi Patrizia Morbini Michele Zorzetto Simona Inghilleri Stefano Tomaselli Patrizia Mangiarotti Federica Meloni Isa Cerveri Giulia Maria Stella |
| author_sort | Matteo Bosio |
| collection | DOAJ |
| description | Abstract Background Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, mainly associated with work or environmental exposure to asbestos. MPM’s molecular profile is largerly unexplored and effective therapies are still lacking. MPM rarely harbours those somatic genetic lesions that usually characterize solid epithelial-derived tumors. On this basis, our study aims at investigating MPM epigenetic profile. Methods We here assessed through immunohistochemistry, FISH and methylation specific PCR, the expression of 5-hydroxymethylcytosine (5- hmC) - an epigenetic marker and an important regulator of embryonic development and carcinogenesis - and the methylation status of the promoter of the MTAP gene - encoding for an enzyme involved in the rescue process of methionine and adenine - in two relevant series of FF-PE MPM samples derived from MPM thoracoscopic biopsies. Tissue sampling was performed at diagnosis. Results Within the limitations of the study cohort, the 5-hmC immunophenotype was different among the histological MPM types analysed. In fact, 18% of the epithelial MPMs were negative, 47% weakly positive, and 35% of the cases showed an intense expression of 5-hmC. Sarcomatoid and biphasic MPMs showed intense 5-hmC expression pattern (positive and weakly positive in more than 80% of cases). Among MPM featuring epithelial lineage, none showed methylation of MTAP promoter. Conclusions Mesothelial sarcomatoid tumors featured a methylation profile characterized by a permanent gene silencing. Epithelial MPM methylation profile was in-between that of sarcomatoid MPM and the one of epithelial-derived tumors. MTAP promoter methylation level cannot be considered a suitable biomarker of epithelial MPM arousal. |
| first_indexed | 2024-03-07T17:29:35Z |
| format | Article |
| id | doaj.art-e5287e141abe43d4b4681fcb86c1627d |
| institution | Directory Open Access Journal |
| issn | 2049-6958 |
| language | English |
| last_indexed | 2024-03-07T17:29:35Z |
| publishDate | 2018-08-01 |
| publisher | PAGEPress Publications |
| record_format | Article |
| series | Multidisciplinary Respiratory Medicine |
| spelling | doaj.art-e5287e141abe43d4b4681fcb86c1627d2024-03-02T18:29:04ZengPAGEPress PublicationsMultidisciplinary Respiratory Medicine2049-69582018-08-011311710.1186/s40248-018-0137-45-hydroxymethylcytosine but not MTAP methylation status can stratify malignant pleural mesothelioma based on the lineage of originMatteo Bosio0Elena Salvaterra1Francesca Datturi2Patrizia Morbini3Michele Zorzetto4Simona Inghilleri5Stefano Tomaselli6Patrizia Mangiarotti7Federica Meloni8Isa Cerveri9Giulia Maria Stella10IRCCS Fondazione Policlinico San Matteo- Unit of Respiratory System Diseases, University of Pavia Medical SchoolIRCCS Fondazione Policlinico San Matteo- Unit of Respiratory System Diseases, University of Pavia Medical SchoolIRCCS Fondazione Policlinico San Matteo- Unit of Respiratory System Diseases, University of Pavia Medical SchoolIRCCS Fondazione Policlinico San Matteo- Pathology Unit, University of Pavia Medical SchoolIRCCS Fondazione Policlinico San Matteo- Unit of Respiratory System Diseases, University of Pavia Medical SchoolIRCCS Fondazione Policlinico San Matteo- Unit of Respiratory System Diseases, University of Pavia Medical SchoolIRCCS Fondazione Policlinico San Matteo- Unit of Respiratory System Diseases, University of Pavia Medical SchoolIRCCS Fondazione Policlinico San Matteo- Unit of Respiratory System Diseases, University of Pavia Medical SchoolIRCCS Fondazione Policlinico San Matteo- Unit of Respiratory System Diseases, University of Pavia Medical SchoolIRCCS Fondazione Policlinico San Matteo- Unit of Respiratory System Diseases, University of Pavia Medical SchoolIRCCS Fondazione Policlinico San Matteo- Unit of Respiratory System Diseases, University of Pavia Medical SchoolAbstract Background Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, mainly associated with work or environmental exposure to asbestos. MPM’s molecular profile is largerly unexplored and effective therapies are still lacking. MPM rarely harbours those somatic genetic lesions that usually characterize solid epithelial-derived tumors. On this basis, our study aims at investigating MPM epigenetic profile. Methods We here assessed through immunohistochemistry, FISH and methylation specific PCR, the expression of 5-hydroxymethylcytosine (5- hmC) - an epigenetic marker and an important regulator of embryonic development and carcinogenesis - and the methylation status of the promoter of the MTAP gene - encoding for an enzyme involved in the rescue process of methionine and adenine - in two relevant series of FF-PE MPM samples derived from MPM thoracoscopic biopsies. Tissue sampling was performed at diagnosis. Results Within the limitations of the study cohort, the 5-hmC immunophenotype was different among the histological MPM types analysed. In fact, 18% of the epithelial MPMs were negative, 47% weakly positive, and 35% of the cases showed an intense expression of 5-hmC. Sarcomatoid and biphasic MPMs showed intense 5-hmC expression pattern (positive and weakly positive in more than 80% of cases). Among MPM featuring epithelial lineage, none showed methylation of MTAP promoter. Conclusions Mesothelial sarcomatoid tumors featured a methylation profile characterized by a permanent gene silencing. Epithelial MPM methylation profile was in-between that of sarcomatoid MPM and the one of epithelial-derived tumors. MTAP promoter methylation level cannot be considered a suitable biomarker of epithelial MPM arousal.http://link.springer.com/article/10.1186/s40248-018-0137-4Malignant pleural mesotheliomaCancerEpigeneticsMethylationLineage of origin |
| spellingShingle | Matteo Bosio Elena Salvaterra Francesca Datturi Patrizia Morbini Michele Zorzetto Simona Inghilleri Stefano Tomaselli Patrizia Mangiarotti Federica Meloni Isa Cerveri Giulia Maria Stella 5-hydroxymethylcytosine but not MTAP methylation status can stratify malignant pleural mesothelioma based on the lineage of origin Multidisciplinary Respiratory Medicine Malignant pleural mesothelioma Cancer Epigenetics Methylation Lineage of origin |
| title | 5-hydroxymethylcytosine but not MTAP methylation status can stratify malignant pleural mesothelioma based on the lineage of origin |
| title_full | 5-hydroxymethylcytosine but not MTAP methylation status can stratify malignant pleural mesothelioma based on the lineage of origin |
| title_fullStr | 5-hydroxymethylcytosine but not MTAP methylation status can stratify malignant pleural mesothelioma based on the lineage of origin |
| title_full_unstemmed | 5-hydroxymethylcytosine but not MTAP methylation status can stratify malignant pleural mesothelioma based on the lineage of origin |
| title_short | 5-hydroxymethylcytosine but not MTAP methylation status can stratify malignant pleural mesothelioma based on the lineage of origin |
| title_sort | 5 hydroxymethylcytosine but not mtap methylation status can stratify malignant pleural mesothelioma based on the lineage of origin |
| topic | Malignant pleural mesothelioma Cancer Epigenetics Methylation Lineage of origin |
| url | http://link.springer.com/article/10.1186/s40248-018-0137-4 |
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