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Clonal Evolution Dynamics in Primary and Metastatic Lesions of Pancreatic Neuroendocrine Neoplasms

Background: Data on inter-tumoral heterogeneity and clonal evolution of pancreatic neuroendocrine neoplasms (panNENs) with liver metastasis are limited. The aim of this study was to explore different patterns of clonal evolution of pancreatic neuroendocrine neoplasms with liver metastasis and the po...

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Autores principales: Tong, Zhou, Wang, Lin, Shi, Weiwei, Zeng, Yanwu, Zhang, Hangyu, Liu, Lulu, Zheng, Yi, Chen, Chunlei, Xia, Weiliang, Fang, Weijia, Zhao, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131504/
https://www.ncbi.nlm.nih.gov/pubmed/34026777
http://dx.doi.org/10.3389/fmed.2021.620988
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author Tong, Zhou
Wang, Lin
Shi, Weiwei
Zeng, Yanwu
Zhang, Hangyu
Liu, Lulu
Zheng, Yi
Chen, Chunlei
Xia, Weiliang
Fang, Weijia
Zhao, Peng
author_facet Tong, Zhou
Wang, Lin
Shi, Weiwei
Zeng, Yanwu
Zhang, Hangyu
Liu, Lulu
Zheng, Yi
Chen, Chunlei
Xia, Weiliang
Fang, Weijia
Zhao, Peng
author_sort Tong, Zhou
collection PubMed
description Background: Data on inter-tumoral heterogeneity and clonal evolution of pancreatic neuroendocrine neoplasms (panNENs) with liver metastasis are limited. The aim of this study was to explore different patterns of clonal evolution of pancreatic neuroendocrine neoplasms with liver metastasis and the possible distinctive signaling pathways involved between G2 neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Methods: Tumor tissues of five patients (10 samples) with pancreatic neuroendocrine neoplasms with synchronous liver metastasis were analyzed using next-generation sequencing. PyClone, Gene Ontology, and Reactome pathway enrichment analysis were also applied. Results: Mutated genes varied in individuals, reflecting the inter-tumoral heterogeneity of panNENs. The distribution of subclones varied during tumor metastasis, and different clonal evolution patterns were revealed between NETs and NECs. Gene Ontology and Reactome analyses revealed that in both NETs and NECs, signaling pathways and biological processes shared similarities and differences in the primary and metastatic lesions. In addition, the signaling pathway features were different between NETs and NECs. In the primary lesions, epigenetic changes and post-transcriptional modifications participated in NETs, while FGFR signaling, EGFR signaling, and NTRK2 signaling were largely involved in NECs. Although DNA repair and TP53 regulation were both involved in the metastatic lesions, most of the signaling pathways and biological processes disrupted by the mutated genes were different. Conclusions: Our study revealed spatial inter-tumoral heterogeneity and temporal clonal evolution in PanNENs, providing potential therapeutic targets for further prospective clinical trials.
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spelling pubmed-81315042021-05-20 Clonal Evolution Dynamics in Primary and Metastatic Lesions of Pancreatic Neuroendocrine Neoplasms Tong, Zhou Wang, Lin Shi, Weiwei Zeng, Yanwu Zhang, Hangyu Liu, Lulu Zheng, Yi Chen, Chunlei Xia, Weiliang Fang, Weijia Zhao, Peng Front Med (Lausanne) Medicine Background: Data on inter-tumoral heterogeneity and clonal evolution of pancreatic neuroendocrine neoplasms (panNENs) with liver metastasis are limited. The aim of this study was to explore different patterns of clonal evolution of pancreatic neuroendocrine neoplasms with liver metastasis and the possible distinctive signaling pathways involved between G2 neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Methods: Tumor tissues of five patients (10 samples) with pancreatic neuroendocrine neoplasms with synchronous liver metastasis were analyzed using next-generation sequencing. PyClone, Gene Ontology, and Reactome pathway enrichment analysis were also applied. Results: Mutated genes varied in individuals, reflecting the inter-tumoral heterogeneity of panNENs. The distribution of subclones varied during tumor metastasis, and different clonal evolution patterns were revealed between NETs and NECs. Gene Ontology and Reactome analyses revealed that in both NETs and NECs, signaling pathways and biological processes shared similarities and differences in the primary and metastatic lesions. In addition, the signaling pathway features were different between NETs and NECs. In the primary lesions, epigenetic changes and post-transcriptional modifications participated in NETs, while FGFR signaling, EGFR signaling, and NTRK2 signaling were largely involved in NECs. Although DNA repair and TP53 regulation were both involved in the metastatic lesions, most of the signaling pathways and biological processes disrupted by the mutated genes were different. Conclusions: Our study revealed spatial inter-tumoral heterogeneity and temporal clonal evolution in PanNENs, providing potential therapeutic targets for further prospective clinical trials. Frontiers Media S.A. 2021-05-05 /pmc/articles/PMC8131504/ /pubmed/34026777 http://dx.doi.org/10.3389/fmed.2021.620988 Text en Copyright © 2021 Tong, Wang, Shi, Zeng, Zhang, Liu, Zheng, Chen, Xia, Fang and Zhao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Tong, Zhou
Wang, Lin
Shi, Weiwei
Zeng, Yanwu
Zhang, Hangyu
Liu, Lulu
Zheng, Yi
Chen, Chunlei
Xia, Weiliang
Fang, Weijia
Zhao, Peng
Clonal Evolution Dynamics in Primary and Metastatic Lesions of Pancreatic Neuroendocrine Neoplasms
title Clonal Evolution Dynamics in Primary and Metastatic Lesions of Pancreatic Neuroendocrine Neoplasms
title_full Clonal Evolution Dynamics in Primary and Metastatic Lesions of Pancreatic Neuroendocrine Neoplasms
title_fullStr Clonal Evolution Dynamics in Primary and Metastatic Lesions of Pancreatic Neuroendocrine Neoplasms
title_full_unstemmed Clonal Evolution Dynamics in Primary and Metastatic Lesions of Pancreatic Neuroendocrine Neoplasms
title_short Clonal Evolution Dynamics in Primary and Metastatic Lesions of Pancreatic Neuroendocrine Neoplasms
title_sort clonal evolution dynamics in primary and metastatic lesions of pancreatic neuroendocrine neoplasms
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131504/
https://www.ncbi.nlm.nih.gov/pubmed/34026777
http://dx.doi.org/10.3389/fmed.2021.620988
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