RT info:eu-repo/semantics/article T1 Matched Paired Primary and Recurrent meningiomasPoints to cell death program contributions to Genomic and epigenomic instability along tumor progression A1 San-Miguel, Teresa A1 Megías Vericat, Javier A1 Monleón, Daniel A1 Navarro Cerveró, Lara A1 Muñoz-Hidalgo, Lisandra A1 Montoliu Félix, Carmina A1 Meri-Abad, Marina A1 Roldán, Pedro A1 Cerdá-Nicolás, Miguel A1 López-Ginés, Concha AB Meningioma (MN) is an important cause of disability, and predictive tools for estimating the risk of recurrence are still scarce. The need for objective and cost-effective techniques addressed to this purpose is well known. In this study, we present methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as a friendly method for deepening the understanding of the mechanisms underlying meningioma progression. A large follow-up allowed us to obtain 50 samples, which included the primary tumor of 20 patients in which half of them are suffering one recurrence and the other half are suffering more than one. We histologically characterized the samples and performed MS-MLPA assays validated by FISH to assess their copy number alterations (CNA) and epigenetic status. Interestingly, we determined the increase in tumor instability with higher values of CNA during the progression accompanied by an increase in epigenetic damage. We also found a loss of HIC1 and the hypermethylation of CDKN2B and PTEN as independent prognostic markers. Comparison between grade 1 and higher primary MN’s self-evolution pointed to a central role of GSTP1 in the first stages of the disease. Finally, a high rate of alterations in genes that are related to apoptosis and autophagy, such as DAPK1, PARK2, BCL2, FHIT, or VHL, underlines an important influence on cell-death programs through different pathways. SN 2072-6694 YR 2022 FD 2022 LK http://riull.ull.es/xmlui/handle/915/36191 UL http://riull.ull.es/xmlui/handle/915/36191 LA en DS Repositorio institucional de la Universidad de La Laguna RD 16-may-2024