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Genetic analysis of familial predisposition in the pathogenesis of malignant pleural mesothelioma

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Abstract

Purpose

Mesothelioma is the primary tumor of the mesothelial cell membrane. The most important etiology is asbestos exposure. The development of malignant mesothelioma in very few of the population exposed to asbestos and its frequent occurrence in some families may be significant in terms of genetic predisposition. Again, the presence of relatives with mesothelioma who did not have asbestos contact strengthens this argument. This disease, which has limited treatment options and has a poor prognosis, revealing a genetic predisposition, if any, may prolong survival with early diagnosis and effective treatment.

Methods

Based on the genetic predisposition idea, we diagnosed and followed a total of ten individuals of relatives with mesothelioma. DNA was isolated from peripheral blood and whole genome sequencing analysis was done. Common gene mutations in ten individuals were filtered using bioinformatics. After this filter, from the remaining variants, very rare in the population and damaging mutations are selected.

Results

Eight thousand six hundred and twenty-two common variants have been identified in ten individuals with this analysis. In total, 120 variants were found on 37 genes in 15 chromosomes. These genes are PIK3R4, SLC25A5, ITGB6, PLK2, RAD17, HLA-B, HLA-DRB1, HLA-DQB1, GRM, IL20RA, MAP3K7, RIPK2, and MUC16.

Conclusion

Our finding, PIK3R4 gene, is directly associated with mesothelioma development. Twelve genes, which are associated with cancer, were detected in literature. Additional studies, which scan first-degree relatives of individual, are needed to find the specific gene region.

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Data availability

All research data available at the Eskisehir Osmangazi University Hospital, Department of Neurology. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

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Acknowledgements

This study was partly supported by the Research Fund of Eskişehir Osmangazi University.

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Authors and Affiliations

  1. Department of Chest Disease, Eskisehir City Hospital, 26080, Eskisehir, Turkey

    Muhittin Akarsu

  2. Lung and Pleural Cancers Research and Clinical Center, Eskisehir Osmangazi University, 26040, Eskisehir, Turkey

    Güntülü Ak & Muzaffer Metintaş

  3. Department of Pathology, Faculty of Medicine, Eskisehir Osmangazi University, Meselik Kampusu, 26480, Eskisehir, Turkey

    Emine Dündar

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  1. Muhittin Akarsu
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  2. Güntülü Ak
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  3. Emine Dündar
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  4. Muzaffer Metintaş
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Contributions

MA, GA, MM: conceptualization, data curation, formal analysis MA, GA, MM: investigation methodology, project administration resources MA, GA, MM: software GA, MM, ED: supervision, validation MA, GA: writing—original draft writing—review and editing.

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Correspondence to Muhittin Akarsu.

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Akarsu, M., Ak, G., Dündar, E. et al. Genetic analysis of familial predisposition in the pathogenesis of malignant pleural mesothelioma. J Cancer Res Clin Oncol 149, 7767–7778 (2023). https://doi.org/10.1007/s00432-023-04730-1

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