TY - JOUR
T1 - Intratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression
AU - Mota, Alba
AU - Oltra, Sara S.
AU - Selenica, Pier
AU - Moiola, Cristian Pablo
AU - Casas-Arozamena, Carlos
AU - López-Gil, Carlos
AU - Diaz, Eva
AU - Gatius, Sonia
AU - Ruiz-Miro, María
AU - Calvo, Ana
AU - Rojo-Sebastián, Alejandro
AU - Hurtado Blanco, P
AU - Piñeiro, Health Research Institute of Santiago de Compostela
AU - Colás Ortega, Eva
AU - Gil-Moreno, Antonio
AU - Reis-Filho, Jorge S.
AU - Muinelo-Romay, Laura
AU - Abal Posada, Miguel
AU - Matias-Guiu, Xavier
AU - Weigelt, Britta
AU - Moreno-Bueno, Gema
PY - 2022
Y1 - 2022
N2 - 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
AB - 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
KW - Gynaecological cancer
KW - Cancer genomics
U2 - 10.1038/s41388-022-02221-0
DO - 10.1038/s41388-022-02221-0
M3 - Article
C2 - 35145232
SN - 0950-9232
VL - 41
SP - 1835
EP - 1850
JO - Oncogene
JF - Oncogene
ER -