Bayesian analysis of the rate of spontaneous malignant mesothelioma among BAP1 mutant mice in the absence of asbestos exposure
Abstract Cancers of the mesothelium, such as malignant mesothelioma (MM), historically have been attributed solely to exposure to asbestos. Recent large scale genetic and genomic functional studies now show that approximately 20% of all human mesotheliomas are causally linked to highly penetrant inh...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-84069-w |
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| author | Dahlia M. Nielsen Mei Hsu Michael Zapata Giovanni Ciavarra Leonel van Zyl |
| author_facet | Dahlia M. Nielsen Mei Hsu Michael Zapata Giovanni Ciavarra Leonel van Zyl |
| author_sort | Dahlia M. Nielsen |
| collection | DOAJ |
| description | Abstract Cancers of the mesothelium, such as malignant mesothelioma (MM), historically have been attributed solely to exposure to asbestos. Recent large scale genetic and genomic functional studies now show that approximately 20% of all human mesotheliomas are causally linked to highly penetrant inherited (germline) pathogenic mutations in numerous cancer related genes. The rarity of these mutations in humans makes it difficult to perform statistically conclusive genetic studies to understand their biological effects. This has created a disconnect between functional and epidemiological studies. However, since the molecular pathogenesis of MM in mice accurately recapitulates that of human disease, this disconnect between functional and epidemiological studies can be overcome by using inbred mouse strains that harbor mutation(s) in genes involved in the disease. Most mouse studies have focused on the effect of asbestos exposure, leaving the effects of genetic mutations in the absence of exposure understudied. Here, using existing peer-reviewed studies, we investigate the rate of spontaneous MM among mice with and without germline genetic mutations, in the absence of asbestos exposure. We leveraged these published data to generate a historical control dataset (HCD) to allow us to improve statistical power and account for genetic heterogeneity between studies. Our Bayesian analyses indicate that the odds of spontaneous MM among germline BAP1 mutant mice is substantially larger than that of wildtype mice. These results support the existing biological study findings that mesotheliomas can arise in the presence of pathogenic germline mutations, independently of asbestos exposure. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-ca446476467e425da7062d9164d95c0f2025-01-05T12:17:28ZengNature PortfolioScientific Reports2045-23222025-01-011511910.1038/s41598-024-84069-wBayesian analysis of the rate of spontaneous malignant mesothelioma among BAP1 mutant mice in the absence of asbestos exposureDahlia M. Nielsen0Mei Hsu1Michael Zapata2Giovanni Ciavarra3Leonel van Zyl4Department of Biological Sciences, North Carolina State UniversityArrayXpress, Inc.ArrayXpress, Inc.Lumanity Clinical and RegulatoryArrayXpress, Inc.Abstract Cancers of the mesothelium, such as malignant mesothelioma (MM), historically have been attributed solely to exposure to asbestos. Recent large scale genetic and genomic functional studies now show that approximately 20% of all human mesotheliomas are causally linked to highly penetrant inherited (germline) pathogenic mutations in numerous cancer related genes. The rarity of these mutations in humans makes it difficult to perform statistically conclusive genetic studies to understand their biological effects. This has created a disconnect between functional and epidemiological studies. However, since the molecular pathogenesis of MM in mice accurately recapitulates that of human disease, this disconnect between functional and epidemiological studies can be overcome by using inbred mouse strains that harbor mutation(s) in genes involved in the disease. Most mouse studies have focused on the effect of asbestos exposure, leaving the effects of genetic mutations in the absence of exposure understudied. Here, using existing peer-reviewed studies, we investigate the rate of spontaneous MM among mice with and without germline genetic mutations, in the absence of asbestos exposure. We leveraged these published data to generate a historical control dataset (HCD) to allow us to improve statistical power and account for genetic heterogeneity between studies. Our Bayesian analyses indicate that the odds of spontaneous MM among germline BAP1 mutant mice is substantially larger than that of wildtype mice. These results support the existing biological study findings that mesotheliomas can arise in the presence of pathogenic germline mutations, independently of asbestos exposure.https://doi.org/10.1038/s41598-024-84069-wMesotheliomaAsbestosBAP1Mouse studiesHistorical control dataBayesian statistics |
| spellingShingle | Dahlia M. Nielsen Mei Hsu Michael Zapata Giovanni Ciavarra Leonel van Zyl Bayesian analysis of the rate of spontaneous malignant mesothelioma among BAP1 mutant mice in the absence of asbestos exposure Scientific Reports Mesothelioma Asbestos BAP1 Mouse studies Historical control data Bayesian statistics |
| title | Bayesian analysis of the rate of spontaneous malignant mesothelioma among BAP1 mutant mice in the absence of asbestos exposure |
| title_full | Bayesian analysis of the rate of spontaneous malignant mesothelioma among BAP1 mutant mice in the absence of asbestos exposure |
| title_fullStr | Bayesian analysis of the rate of spontaneous malignant mesothelioma among BAP1 mutant mice in the absence of asbestos exposure |
| title_full_unstemmed | Bayesian analysis of the rate of spontaneous malignant mesothelioma among BAP1 mutant mice in the absence of asbestos exposure |
| title_short | Bayesian analysis of the rate of spontaneous malignant mesothelioma among BAP1 mutant mice in the absence of asbestos exposure |
| title_sort | bayesian analysis of the rate of spontaneous malignant mesothelioma among bap1 mutant mice in the absence of asbestos exposure |
| topic | Mesothelioma Asbestos BAP1 Mouse studies Historical control data Bayesian statistics |
| url | https://doi.org/10.1038/s41598-024-84069-w |
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