Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/181320
Full metadata record
DC FieldValueLanguage
dc.contributor.authorFarré, Lourdes-
dc.contributor.authorSanz Linares, Gabriela-
dc.contributor.authorRuiz Xivillé, Neus-
dc.contributor.authorCastro de Moura, Manuel-
dc.contributor.authorMartín Tejera, Juan F.-
dc.contributor.authorGonçalves Ribeiro, Samuel-
dc.contributor.authorMartínez Iniesta, María-
dc.contributor.authorCalaf, Monica-
dc.contributor.authorMosquera Mayo, José Luís-
dc.contributor.authorMartín Subero, José Ignacio-
dc.contributor.authorGranada, Isabel-
dc.contributor.authorEsteller, Manel-
dc.contributor.authorDomingo Domènech, Eva-
dc.contributor.authorCliment, Fina-
dc.contributor.authorVillanueva Garatachea, Alberto-
dc.contributor.authorSureda, Anna-
dc.date.accessioned2021-11-18T14:14:28Z-
dc.date.available2021-11-18T14:14:28Z-
dc.date.issued2021-07-01-
dc.identifier.urihttp://hdl.handle.net/2445/181320-
dc.description.abstractExtramedullary multiple myeloma (EMM) has an overall survival of 6 months and occurs in 20% of multiple myeloma (MM) patients. Genetic and epigenetic mechanisms involved in EMM and the therapeutic role of new agents for MM are not well established. Besides, well-characterized preclinical models for EMM are not available. Herein, a patient-derived orthotopic xenograft (PDOX) was generated from a patient with an aggressive EMM to study in-depth genetic and epigenetic events, and drug responses related to extramedullary disease. A fresh punch of an extramedullary cutaneous lesion was orthotopically implanted in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ(NSG) mouse. The PDOX mimicked histologic and phenotypic features of the tumor of the patient. Cytogenetic studies revealed a hyperploid genome with multiple genetic poor-prognosis alterations. Copy number alterations (CNAs) were detected in all chromosomes. The IGH translocation t(14;16)(q32;q23)IGH/MAF was already observed at the medullary stage and a new one, t(10;14)(p?11-12;q32), was observed only with extramedullary disease and could be eventually related to EMM progression in this case. Exome sequencing showed 24 high impact single nucleotide variants and 180 indels. From the genes involved, only TP53 was previously described as a driver in MM. A rather balanced proportion of hyper/hypomethylated sites different to previously reported widespread hypomethylation in MM was also observed. Treatment with lenalidomide, dexamethasone and carfilzomib showed a tumor weight reduction of 90% versus non-treated tumors, whereas treatment with the anti-CD38 antibody daratumumab showed a reduction of 46%. The generation of PDOX from a small EMM biopsy allowed us to investigate in depth the molecular events associated with extramedullary disease in combination with drug testing.-
dc.format.mimetypeapplication/pdf-
dc.language.isoeng-
dc.publisherThe Company of Biologists-
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1242/dmm.048223-
dc.relation.ispartofDisease Models & Mechanisms, 2021-
dc.relation.urihttps://doi.org/10.1242/dmm.048223-
dc.rightscc-by (c) Farré, Lourdes et al., 2021-
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.sourceArticles publicats en revistes (Ciències Fisiològiques)-
dc.subject.classificationEpigenètica-
dc.subject.classificationMieloma múltiple-
dc.subject.classificationPacients-
dc.subject.otherEpigenetics-
dc.subject.otherMultiple myeloma-
dc.subject.otherPacients-
dc.titleExtramedullary multiple myeloma patient-derived orthotopic xenograft with a highly altered genome: combined molecular and therapeutic studies-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.identifier.idgrec716106-
dc.date.updated2021-11-18T10:22:56Z-
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess-
dc.identifier.pmid33988237-
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Files in This Item:
File Description SizeFormat 
dmm048223.pdf11.69 MBAdobe PDFView/Open


This item is licensed under a Creative Commons License Creative Commons