Intratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression
Mota, Alba (Universidad Autónoma de Madrid. Departamento de Bioquímica)
Oltra, Sara S. (Centro de Investigación Biomédica en Red de Cáncer)
Selenica, Pier (Memorial Sloan Kettering Cancer Center)
Moiola, Cristian Pablo (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Casas-Arozamena, Carlos (Instituto de Investigación Sanitaria de Santiago (IDIS))
López-Gil, Carlos (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Diaz, Eva (MD Anderson International Foundation)
Gatius, Sonia (Hospital Arnau de Vilanova (València))
Ruiz-Miro, María (Biobank (Lleida))
Calvo, Ana (Hospital Arnau de Vilanova (Lleida, Catalunya))
Rojo-Sebastián, Alejandro (MD Anderson Cancer Center)
Hurtado Blanco, P (Instituto de Investigación Sanitaria de Santiago (IDIS))
Piñeiro, Health Research Institute of Santiago de Compostela
Colás Ortega, Eva (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Gil-Moreno, Antonio 1965- (Hospital Universitari Vall d'Hebron)
Reis-Filho, Jorge S. (Memorial Sloan Kettering Cancer Center.)
Muinelo-Romay, Laura (Instituto de Investigación Sanitaria de Santiago (IDIS))
Abal Posada, Miguel (Instituto de Investigación Sanitaria de Santiago (IDIS))
Matias-Guiu, Xavier (Universitat de Lleida)
Weigelt, Britta (Memorial Sloan Kettering Cancer Center. Department of Pathology)
Moreno-Bueno, Gema (Centro de Investigación Biomédica en Red de Cáncer)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	Analyzing 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.
Grants:	Ministerio de Economía y Competitividad CB16/12/00295 Ministerio de Economía y Competitividad CB16/12/00328 Ministerio de Economía y Competitividad PT13/0010/0014
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Gynaecological cancer ; Cancer genomics
Published in:	Oncogene, Vol. 41 (february 2022) , p. 1835-1850, ISSN 1476-5594

DOI: 10.1038/s41388-022-02221-0
PMID: 35145232

16 p, 5.4 MB

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