Intratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression Journal Article
| Authors: | Mota, A.; Oltra, S. S.; Selenica, P.; Moiola, C. P.; Casas-Arozamena, C.; López-Gil, C.; Diaz, E.; Gatius, S.; Ruiz-Miro, M.; Calvo, A.; Rojo-Sebastián, A.; Hurtado, P.; Piñeiro, R.; Colas, E.; Gil-Moreno, A.; Reis-Filho, J. S.; Muinelo-Romay, L.; Abal, M.; Matias-Guiu, X.; Weigelt, B.; Moreno-Bueno, G. |
| Article Title: | Intratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression |
| 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. © 2022, The Author(s). |
| Keywords: | clinical article; human tissue; promoter region; somatic mutation; clinical feature; cancer recurrence; cancer growth; endometrium cancer; genetic association; risk factor; comparative genomic hybridization; genetic heterogeneity; copy number variation; phylogenetic tree; clonal evolution; cancer prognosis; human; female; article; whole exome sequencing |
| Journal Title: | Oncogene |
| Volume: | 41 |
| Issue: | 13 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2022-03-25 |
| Start Page: | 1835 |
| End Page: | 1850 |
| Language: | English |
| DOI: | 10.1038/s41388-022-02221-0 |
| PUBMED: | 35145232 |
| PROVIDER: | scopus |
| PMCID: | PMC8956509 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 25 April 2022 -- Source: Scopus |
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189Selenica
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