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Examination of genetic susceptibility in radiation-associated meningioma

ABSTRACT: Examination of genetic susceptibility in radiation-associated meningioma

PROVIDER: PRJNA858536 | ENA |

REPOSITORIES: ENA

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Examination of genetic susceptibility in radiation-associated meningioma

Project description:Examination of genetic susceptibility in radiation-associated meningioma

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Examination of Genetic Susceptibility in Radiation-Associated Meningioma.

Project description:Previous epidemiological studies have demonstrated elevated susceptibility to ionizing radiation in some families, thus suggesting the presence of genetic components that conferred increased rate of radiation-associated meningioma (RAM). In this study, we exome-sequenced and investigated the segregation pattern of rare deleterious variants in 11 RAM pedigrees. In addition, we performed a rare-variant association analysis in 92 unrelated familial cases of RAM that were ancestry-matched with 88 meningioma-free controls. In the pedigree analysis, we found that each family carried mostly a unique set of rare deleterious variants. A follow-up pathway analysis of the union of the genes that segregated within each of the 11 pedigrees identified a single statistically significant (q value = 7.90E-04) "ECM receptor interaction" set. In the case-control association analysis, we observed no statistically significant variants or genes after multiple testing correction; however, examination of ontological categories of the genes that associated with RAM at nominal P values <0.01 identified biologically relevant pathways such as DNA repair, cell cycle and apoptosis. These results suggest that it is unlikely that a small number of highly penetrant genes are involved in the pathogenesis of RAM. Substantially larger studies are needed to identify genetic risk variants and genes in RAM.

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Genomic profiling of anaplastic meningioma identifies recurrent genetic alterations with relevance to lower-grade meningioma

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