Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/54445 |
Resumo: | © The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
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Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Colorectal cancer (CRC) is a highly diverse disease, where different genomic instability pathways shape genetic clonal diversity and tumor microenvironment. Although intra-tumor heterogeneity has been characterized in primary tumors, its origin and consequences in CRC outcome is not fully understood. Therefore, we assessed intra- and inter-tumor heterogeneity of a prospective cohort of 136 CRC samples. We demonstrate that CRC diversity is forged by asynchronous forms of molecular alterations, where mutational and chromosomal instability collectively boost CRC genetic and microenvironment intra-tumor heterogeneity. We were able to depict predictor signatures of cancer-related genes that can foresee heterogeneity levels across the different tumor consensus molecular subtypes (CMS) and primary tumor location. Finally, we show that high genetic and microenvironment heterogeneity are associated with lower metastatic potential, whereas late-emerging copy number variations favor metastasis development and polyclonal seeding. This study provides an exhaustive portrait of the interplay between genetic and microenvironment intra-tumor heterogeneity across CMS subtypes, depicting molecular events with predictive value of CRC progression and metastasis development.This work was financed by national funds from FCT - Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences - UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB. This research was also funded by: PTDC/MED-ONC/28660/2017 from Fundação para a Ciência e Tecnologia (FCT) to A.R.G. A.R.G is recipient of Researcher Grant CEECIND/02699/2017 from FCT. The biobanking of CRC samples from Hospital Santa Maria, Lisbon, Portugal was supported by FCT research grant PIC/IC/82821/2007. This work was produced with the support of INCD funded by FCT and FEDER under the project 22153-01/SAICT/2016.Springer NatureRepositório da Universidade de LisboaSobral, DanielMartins, MartaKaplan, ShannonGolkaram, MahdiSalmans, MichaelKhan, NafeesaVijayaraghavan, RaakheeCasimiro, SandraFernandes, AfonsoBorralho, PaulaFerreira, CristinaPinto, RuiMarques, CatarinaCosta, Ana LúciaZhang, ShilePawlowski, TraciGodsey, JimMansinho, AndréMacedo, DanielaLobo-Martins, SoraiaFilipe, PedroEsteves, RuiCoutinho, JoaoCosta, Paulo M.Ramires, AfonsoAldeia, FernandoQuintela, AntónioSo, AlexLiu, LiGrosso, Ana RitaCosta, Luis2022-09-13T11:18:47Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/54445engCommun Biol. 2022 Sep 9;5(1):93710.1038/s42003-022-03884-x2399-3642info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:00:49Zoai:repositorio.ul.pt:10451/54445Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:05:16.132236Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development |
title |
Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development |
spellingShingle |
Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development Sobral, Daniel |
title_short |
Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development |
title_full |
Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development |
title_fullStr |
Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development |
title_full_unstemmed |
Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development |
title_sort |
Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development |
author |
Sobral, Daniel |
author_facet |
Sobral, Daniel Martins, Marta Kaplan, Shannon Golkaram, Mahdi Salmans, Michael Khan, Nafeesa Vijayaraghavan, Raakhee Casimiro, Sandra Fernandes, Afonso Borralho, Paula Ferreira, Cristina Pinto, Rui Marques, Catarina Costa, Ana Lúcia Zhang, Shile Pawlowski, Traci Godsey, Jim Mansinho, André Macedo, Daniela Lobo-Martins, Soraia Filipe, Pedro Esteves, Rui Coutinho, Joao Costa, Paulo M. Ramires, Afonso Aldeia, Fernando Quintela, António So, Alex Liu, Li Grosso, Ana Rita Costa, Luis |
author_role |
author |
author2 |
Martins, Marta Kaplan, Shannon Golkaram, Mahdi Salmans, Michael Khan, Nafeesa Vijayaraghavan, Raakhee Casimiro, Sandra Fernandes, Afonso Borralho, Paula Ferreira, Cristina Pinto, Rui Marques, Catarina Costa, Ana Lúcia Zhang, Shile Pawlowski, Traci Godsey, Jim Mansinho, André Macedo, Daniela Lobo-Martins, Soraia Filipe, Pedro Esteves, Rui Coutinho, Joao Costa, Paulo M. Ramires, Afonso Aldeia, Fernando Quintela, António So, Alex Liu, Li Grosso, Ana Rita Costa, Luis |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Sobral, Daniel Martins, Marta Kaplan, Shannon Golkaram, Mahdi Salmans, Michael Khan, Nafeesa Vijayaraghavan, Raakhee Casimiro, Sandra Fernandes, Afonso Borralho, Paula Ferreira, Cristina Pinto, Rui Marques, Catarina Costa, Ana Lúcia Zhang, Shile Pawlowski, Traci Godsey, Jim Mansinho, André Macedo, Daniela Lobo-Martins, Soraia Filipe, Pedro Esteves, Rui Coutinho, Joao Costa, Paulo M. Ramires, Afonso Aldeia, Fernando Quintela, António So, Alex Liu, Li Grosso, Ana Rita Costa, Luis |
description |
© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-09-13T11:18:47Z 2022 2022-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/54445 |
url |
http://hdl.handle.net/10451/54445 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Commun Biol. 2022 Sep 9;5(1):937 10.1038/s42003-022-03884-x 2399-3642 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
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