Intratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression.
Intratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression.
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DOI：
10.1038/s41388-022-02221-0
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发表时间：
2022-03
期刊：
影响因子：
8
通讯作者：
Moreno-Bueno G
中科院分区：
文献类型：
--
作者：
Mota A;Oltra SS;Selenica P;Moiola CP;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 JS;Muinelo-Romay L;Abal M;Matias-Guiu X;Weigelt B;Moreno-Bueno G
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.
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通讯作者：
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通讯作者：
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