3 research outputs found
EpiGe: A machine-learning strategy for rapid classification of medulloblastoma using PCR-based methyl-genotyping
Molecular classification of medulloblastoma is critical for the treatment of this brain tumor. Array-based DNA methylation profiling has emerged as a powerful approach for brain tumor classification. However, this technology is currently not widely available. We present a machine-learning decision support system (DSS) that enables the classification of the principal molecular groupsâWNT, SHH, and non-WNT/non-SHHâdirectly from quantitative PCR (qPCR) data. We propose a framework where the developed DSS appears as a user-friendly web-applicationâEpiGe-Appâthat enables automated interpretation of qPCR methylation data and subsequent molecular group prediction. The basis of our classification strategy is a previously validated six-cytosine signature with subgroup-specific methylation profiles. This reduced set of markers enabled us to develop a methyl-genotyping assay capable of determining the methylation status of cytosines using qPCR instruments. This study provides a comprehensive approach for rapid classification of clinically relevant medulloblastoma groups, using readily accessible equipment and an easy-to-use web-application.The study was supported by Associations of Parents and Families of Children with Cancer and by funding of the Spanish Ministry of for Science, Innovation and University (grant PI20/00519; PI CL) and the Foundation La MaratĂł TV3 (grant 201921-30; PI CL). We acknowledge the multidisciplinary team who helped in the molecular analyses and care of patients, and the BioBank Hospital Sant Joan de DĂ©u of the Spanish BioBank Network for sample procurement. We also acknowledge Marta Fortuny for communication strategy advice and Eduard Puig for legal assistance and data protection regulations. Authors acknowledge the SJD Fundraising Team.Peer ReviewedArticle signat per 23 autors/es: Soledad GĂłmez-GonzĂĄlez, Joshua Llano, Marta Garcia, Alicia Garrido-Garcia, Mariona Suñol, Isadora Lemos, Sara Perez-Jaume, Noelia Salvador, Nagore Gene-Olaciregui, Raquel Arnau GalĂĄn, Vicente Santa-MarĂa, Marta Perez-Somarriba, Alicia Castañeda, JosĂ© Hinojosa, Ursula Winter, Francisco Barbosa Moreira, Fabiana Lubieniecki, Valeria Vazquez, Jaume Mora, Ofelia Cruz, AndrĂ©s Morales La Madrid, Alexandre Perera, Cinzia Lavarino.Postprint (published version
High prevalence of BRAFV600E in patients with cholestasis, sclerosing cholangitis or liver fibrosis secondary to Langerhans cell histiocytosis
Targeted therapies with MAPK inhibitors have proven to modulate the clinical manifestations of patients with Langerhans cell histiocytosis (LCH). We explored the presence of BRAFV600E mutation in our cohort of patients with LCH and cholestasis, sclerosing cholangitis, or liver fibrosis that presented resistance to chemotherapy. The BRAFV600E mutation was detected either in the diagnosis (skin and bone) or liver biopsy in our cohort of 13 patients. Thus, we observed a high incidence of BRAFV600E mutation in 100% either in diagnostic biopsy (skin and bone) or liver biopsy in patients with progressive liver disease, sequela, or liver transplant requirement.Fil: Carrere, Xiomara. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; ArgentinaFil: Pinto, NicolĂĄs Alejandro. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Gene Olaciregui, Nagore. Hospital Sant Joan de DĂ©u; EspañaFil: Galluzzo, Laura. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; ArgentinaFil: Rossetti, Estefania. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; ArgentinaFil: Celis Passini, Veronica. Hospital Sant Joan de DĂ©u; EspañaFil: Salvador Marcos, Noelia. Hospital Sant Joan de DĂ©u; EspañaFil: Chantada, Guillermo Luis. Hospital Sant Joan de DĂ©u; España. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Braier, Jorge. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; ArgentinaFil: Lavarino, Cinzia. Hospital Sant Joan de DĂ©u; EspañaFil: Felizzia, Guido. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; Argentin
Assessment of geneâdisease associations and recommendations for genetic testing for somatic variants in vascular anomalies by VASCERN-VASCA
International audienceAbstract Background Vascular anomalies caused by somatic (postzygotic) variants are clinically and genetically heterogeneous diseases with overlapping or distinct entities. The genetic knowledge in this field is rapidly growing, and genetic testing is now part of the diagnostic workup alongside the clinical, radiological and histopathological data. Nonetheless, access to genetic testing is still limited, and there is significant heterogeneity across the approaches used by the diagnostic laboratories, with direct consequences on test sensitivity and accuracy. The clinical utility of genetic testing is expected to increase progressively with improved theragnostics, which will be based on information about the efficacy and safety of the emerging drugs and future molecules. The aim of this study was to make recommendations for optimising and guiding the diagnostic genetic testing for somatic variants in patients with vascular malformations. Results Physicians and lab specialists from 11 multidisciplinary European centres for vascular anomalies reviewed the genes identified to date as being involved in non-hereditary vascular malformations, evaluated geneâdisease associations, and made recommendations about the technical aspects for identification of low-level mosaicism and variant interpretation. A core list of 24 genes were selected based on the current practices in the participating laboratories, the ISSVA classification and the literature. In total 45 geneâphenotype associations were evaluated: 16 were considered definitive, 16 strong, 3 moderate, 7 limited and 3 with no evidence. Conclusions This work provides a detailed evidence-based view of the geneâdisease associations in the field of vascular malformations caused by somatic variants. Knowing both the geneâphenotype relationships and the strength of the associations greatly help laboratories in data interpretation and eventually in the clinical diagnosis. This study reflects the state of knowledge as of mid-2023 and will be regularly updated on the VASCERN-VASCA website (VASCERN-VASCA, https://vascern.eu/groupe/vascular-anomalies/ )