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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorMota Jimenez, Alba
dc.contributor.authorOltra, Sara S
dc.contributor.authorSelenica, Pier
dc.contributor.authorMoiola, Cristian Pablo
dc.contributor.authorCasas-Arozamena, Carlos
dc.contributor.authorLopez Gil, Carlos
dc.contributor.authorRojo Sebastian, Alejandro
dc.contributor.authorColas Ortega, Eva
dc.contributor.authorGil Moreno, Antonio
dc.date.accessioned2022-08-19T09:33:44Z
dc.date.available2022-08-19T09:33:44Z
dc.date.issued2022-03-25
dc.identifier.citationMota A, Oltra SS, Selenica P, Moiola CP, Casas-Arozamena C, López-Gil C, et al. Intratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression. Oncogene. 2022 Mar 25;41:1835–50.
dc.identifier.issn1476-5594
dc.identifier.urihttp://hdl.handle.net/11351/8023
dc.descriptionEndometrial cancer; Clonal evolution; Mutation
dc.description.abstractAnalyzing different tumor regions by next generation sequencing allows the assessment of intratumor genetic heterogeneity (ITGH), a phenomenon that has been studied widely in some tumor types but has been less well explored in endometrial carcinoma (EC). In this study, we sought to characterize the spatial and temporal heterogeneity of 9 different ECs using whole-exome sequencing, and by performing targeted sequencing validation of the 42 primary tumor regions and 30 metastatic samples analyzed. In addition, copy number alterations of serous carcinomas were assessed by comparative genomic hybridization arrays. From the somatic mutations, identified by whole-exome sequencing, 532 were validated by targeted sequencing. Based on these data, the phylogenetic tree reconstructed for each case allowed us to establish the tumors’ evolution and correlate this to tumor progression, prognosis, and the presence of recurrent disease. Moreover, we studied the genetic landscape of an ambiguous EC and the molecular profile obtained was used to guide the selection of a potential personalized therapy for this patient, which was subsequently validated by preclinical testing in patient-derived xenograft models. Overall, our study reveals the impact of analyzing different tumor regions to decipher the ITGH in ECs, which could help make the best treatment decision.
dc.language.isoeng
dc.publisherSpringer Nature
dc.relation.ispartofseriesOncogene;41
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectEndometri - Càncer - Aspectes genètics
dc.subject.meshEndometrial Neoplasms
dc.subject.mesh/genetics
dc.subject.meshGenetic Heterogeneity
dc.titleIntratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1038/s41388-022-02221-0
dc.subject.decsneoplasias endometriales
dc.subject.decs/genética
dc.subject.decsheterogeneidad genética
dc.relation.publishversionhttps://doi.org/10.1038/s41388-022-02221-0
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Mota A] MD Anderson International Foundation, Madrid, Spain. Biochemistry Department, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM), IdiPaz, Madrid, Spain. [Oltra SS] MD Anderson International Foundation, Madrid, Spain. Biochemistry Department, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM), IdiPaz, Madrid, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. [Selenica P] Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA. [Moiola CP, Colas E] Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Casas-Arozamena C] Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago de Compostela (IDIS), University Hospital of Santiago de Compostela (SERGAS), Santiago de Compostela, Spain. [López-Gil C] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Rojo-Sebastián A] Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. MD Anderson Cancer Center, Madrid, Spain. [Gil-Moreno A] Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Ginecologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain
dc.identifier.pmid35145232
dc.identifier.wos000754012300003
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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