Intratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression

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dc.contributor.authorMota, Alba
dc.contributor.authorOltra, Sara S.
dc.contributor.authorSelenica, Pier
dc.contributor.authorMoiola, Cristian P.
dc.contributor.authorCasas Arozamena, Carlos
dc.contributor.authorLópez-Gil, Carlos
dc.contributor.authorDíaz, Eva
dc.contributor.authorGatius Calderó, Sònia
dc.contributor.authorRuiz Miró, Maria
dc.contributor.authorCalvo, Ana
dc.contributor.authorRojo Sebastián, Alejandro
dc.contributor.authorHurtado, Pablo
dc.contributor.authorPiñeiro, Roberto
dc.contributor.authorColás, Eva
dc.contributor.authorGil-Moreno, Antonio
dc.contributor.authorReis-Filho, Jorge S.
dc.contributor.authorMuinelo-Romay, Laura
dc.contributor.authorAbal, Miguel
dc.contributor.authorMatias-Guiu, Xavier
dc.contributor.authorWeigelt, Britta
dc.contributor.authorMoreno Bueno, Gema
dc.date.accessioned2022-05-04T09:24:34Z
dc.date.available2022-05-04T09:24:34Z
dc.date.issued2022
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.ca_ES
dc.identifier.doihttps://doi.org/10.1038/s41388-022-02221-0
dc.identifier.issn0950-9232
dc.identifier.issn1476-5594
dc.identifier.urihttp://hdl.handle.net/10459.1/83214
dc.language.isoengca_ES
dc.publisherSpringer Natureca_ES
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1038/s41388-022-02221-0ca_ES
dc.relation.ispartofOncogene, 2022, v. 41, p. 1835–1850ca_ES
dc.rightscc-by (c) Authors, 2022ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectClonal Evolutionca_ES
dc.subjectComparative Genomic Hybridizationca_ES
dc.subjectGeneticca_ES
dc.titleIntratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progressionca_ES
dc.typeinfo:eu-repo/semantics/articleca_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionca_ES
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