Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development

Detalhes bibliográficos
Autor(a) principal: Sobral, Daniel
Data de Publicação: 2022
Outros Autores: 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
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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spelling 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
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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
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dc.publisher.none.fl_str_mv Springer Nature
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