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. 2023 Aug;149(10):7767-7778.
doi: 10.1007/s00432-023-04730-1. Epub 2023 Apr 7.

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

Muhittin Akarsu  1 , Güntülü Ak  2 , Emine Dündar  3 , Muzaffer Metintaş  2
Affiliations

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

Muhittin Akarsu et al. J Cancer Res Clin Oncol. 2023 Aug.

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.

Keywords: Familial predisposition; Genetics; Genome sequencing; Mesothelioma.

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Conflict of interest statement

All the authors declare have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Pedigree of Family A
Fig. 2
Fig. 2
Pedigree of Family B
Fig. 3
Fig. 3
Pedigree of Family C
Fig. 4
Fig. 4
Pedigree of Family D
Fig. 5
Fig. 5
Graph showing the types of base-level variants detected in genes and which type of mutation they cause
Fig. 6
Fig. 6
Type of mutations detected in genes
Fig. 7
Fig. 7
Mutation results in genes associated with cancer development and pathways
Fig. 8
Fig. 8
Common gene mutation types observed in ten individuals
See this image and copyright information in PMC

References

    1. Adams S, Valchanova RS, Munz B (2010) RIP2: a novel player in the regulation of keratinocyte proliferation and cutaneous wound repair? Exp Cell Res 316(5):728–736 - PubMed
    1. Aithal A et al (2018) MUC16 as a novel target for cancer therapy. Expert Opin Ther Targets 22(8):675–686 - PMC - PubMed
    1. Ak G et al (2009) Prognostic factors according to the treatment schedule in malignant pleural mesothelioma. J Thorac Oncol 4(11):1425–1430 - PubMed
    1. Aptsiauri N et al (2007) Role of altered expression of HLA class I molecules in cancer progression. In: Ren T (ed) Immune-mediated diseases. Springer, pp 123–131 - PubMed
    1. Bao S et al (2001) ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses. Nature 411(6840):969–974 - PubMed