Intratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression

Alba Mota, Sara S. Oltra, Pier Selenica, Cristian Pablo Moiola, Carlos Casas-Arozamena, Carlos López-Gil, Eva Diaz, Sonia Gatius, María Ruiz-Miro, Ana Calvo, Alejandro Rojo-Sebastián, P Hurtado Blanco, Health Research Institute of Santiago de Compostela Piñeiro, Eva Colás Ortega, Antonio Gil-Moreno, Jorge S. Reis-Filho, Laura Muinelo-Romay, Miguel Abal Posada, Xavier Matias-Guiu, Britta WeigeltGema Moreno-Bueno

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Resum

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
Idioma originalAnglès
Pàgines (de-a)1835-1850
Nombre de pàgines16
RevistaOncogene
Volum41
DOIs
Estat de la publicacióPublicada - 2022

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