dc.contributor.author | Mata, Elena | |
dc.contributor.author | Díaz-López, Antonio | |
dc.contributor.author | Martín-Moreno, Ana María | |
dc.contributor.author | Sánchez-Beato, Margarita | |
dc.contributor.author | Varela, Ignacio | |
dc.contributor.author | Mestre, María J. | |
dc.contributor.author | Santonja, Carlos | |
dc.contributor.author | Burgos, Fernando | |
dc.contributor.author | Menárguez, Javier | |
dc.contributor.author | Estévez, Mónica | |
dc.contributor.author | Provencio Pulla, Mariano | |
dc.contributor.author | Sánchez-Espiridión, Beatriz | |
dc.contributor.author | Díaz, Eva | |
dc.contributor.author | Montalbán, Carlos | |
dc.contributor.author | Piris, Miguel A. | |
dc.contributor.author | García, Juan F. | |
dc.contributor.other | UAM. Departamento de Medicina | es_ES |
dc.date.accessioned | 2018-02-08T15:12:14Z | |
dc.date.available | 2018-02-08T15:12:14Z | |
dc.date.issued | 2017-11-30 | |
dc.identifier.citation | Oncotarget 8.67 (2017): 111386-111395 | en_US |
dc.identifier.issn | 1949-2553 | es_ES |
dc.identifier.uri | http://hdl.handle.net/10486/681138 | |
dc.description.abstract | Defining the mutational landscape of classic Hodgkin lymphoma is still a major research goal. New targeted next-generation sequencing (NGS) techniques may identify pathogenic mechanisms and new therapeutic opportunities related to this disease. We describe the mutational profile of a series of 57 cHL cases, enriched in Hodgkin and Reed-Sternberg (HRS) cells. Overall, the results confirm the presence of strong genomic heterogeneity. However, several variants were consistently detected in genes related to relevant signaling pathways, such as GM-CSF/IL-3, CBP/EP300, JAK/STAT, NF-kappaB, and numerous variants of genes affecting the B-cell receptor (BCR) pathway, such as BTK, CARD11, BCL10, among others. This unexpectedly high prevalence of mutations affecting the BCR pathway suggests some requirement for active BCR signaling for cHL cell viability. Additionally, incubation of a panel of cHL cellular models with selective BTK inhibitors in vitro constrains cell proliferation and causes cell death. Our results indicate new pathogenic mechanisms and therapeutic opportunities in this disease | en_US |
dc.description.sponsorship | This work was supported by grants from the Plan Nacional de I+D+I co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), PI12/1832, RTICC RD06/0020/0107, PI14/00221, CIBER de Cancer, PIE15/0081 and PI16/01294, the Spanish Association for Cancer Research (AECC), and by funds of the U.T M.D. Anderson Cancer Center. MSB currently holds a Miguel Servet contract (CP11/00018 and CPII16/00024) from the ISCIII- MINECO-AES-FEDER (P.N.I+D+I 2008-2011), Spain | en_US |
dc.format.extent | 10 pag. | es_ES |
dc.format.mimetype | application/pdf | en |
dc.language.iso | eng | en |
dc.publisher | Impact Journals | en_US |
dc.relation.ispartof | Oncotarget | es_ES |
dc.rights | © 2017 Mata et al. | es_ES |
dc.subject.other | Mutational analysis | en_US |
dc.subject.other | Hodgkin lymphoma | en_US |
dc.subject.other | B-cell receptor | en_US |
dc.subject.other | BTK | en_US |
dc.subject.other | Therapeutic target | en_US |
dc.title | Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets | en_US |
dc.type | article | en |
dc.subject.eciencia | Medicina | es_ES |
dc.relation.publisherversion | https://doi.org/10.18632/oncotarget.22799 | es_ES |
dc.identifier.doi | 10.18632/oncotarget.22799 | es_ES |
dc.identifier.publicationfirstpage | 111386 | es_ES |
dc.identifier.publicationissue | 67 | es_ES |
dc.identifier.publicationlastpage | 111395 | es_ES |
dc.identifier.publicationvolume | 6 | es_ES |
dc.relation.projectID | Gobierno de España. PI12/1832 | es_ES |
dc.relation.projectID | Gobierno de España. RTICC RD06/0020/0107 | es_ES |
dc.relation.projectID | Gobierno de España. PIE15/0081 | es_ES |
dc.relation.projectID | Gobierno de España. PI16/01294 | es_ES |
dc.type.version | info:eu-repo/semantics/publishedVersion | en |
dc.rights.cc | Reconocimiento | es_ES |
dc.rights.accessRights | openAccess | en |
dc.authorUAM | Provencio Pulla, Mariano (262376) | |
dc.facultadUAM | Facultad de Medicina | |