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, Abreu, Catarina, Costa, Ana Lúcia, Zhang, Shile, Pawlowski, Traci, Godsey, Jim, Mansinho, André, Macedo, Daniela, Lobo-Martins, Soraia, Filipe, Pedro, Esteves, Rui, Coutinho, João, Costa, Paulo Matos, 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/10362/145912
Resumo: We thank João Neto and remaining Computational Multi-Omics Lab members at UCIBIO for their helpful comments and suggestions. © 2022. The Author(s).
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spelling Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic developmentColorectal Neoplasms/geneticsDNA Copy Number VariationsHumansOncogenesProspective StudiesTumor Microenvironment/geneticsSDG 3 - Good Health and Well-beingWe thank João Neto and remaining Computational Multi-Omics Lab members at UCIBIO for their helpful comments and suggestions. © 2022. The Author(s).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.UCIBIO - Applied Molecular Biosciences UnitDCV - Departamento de Ciências da VidaRUNSobral, DanielMartins, MartaKaplan, ShannonGolkaram, MahdiSalmans, MichaelKhan, NafeesaVijayaraghavan, RaakheeCasimiro, SandraFernandes, AfonsoBorralho, PaulaFerreira, CristinaPinto, RuiAbreu, CatarinaCosta, Ana LúciaZhang, ShilePawlowski, TraciGodsey, JimMansinho, AndréMacedo, DanielaLobo-Martins, SoraiaFilipe, PedroEsteves, RuiCoutinho, JoãoCosta, Paulo MatosRamires, AfonsoAldeia, FernandoQuintela, AntónioSo, AlexLiu, LiGrosso, Ana RitaCosta, Luis2022-11-30T22:11:55Z2022-09-092022-09-09T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article14application/pdfhttp://hdl.handle.net/10362/145912engPURE: 46643886https://doi.org/10.1038/s42003-022-03884-xinfo: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:RCAAP2024-05-22T18:07:03Zoai:run.unl.pt:10362/145912Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-22T18:07:03Repositório 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
Colorectal Neoplasms/genetics
DNA Copy Number Variations
Humans
Oncogenes
Prospective Studies
Tumor Microenvironment/genetics
SDG 3 - Good Health and Well-being
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
Abreu, Catarina
Costa, Ana Lúcia
Zhang, Shile
Pawlowski, Traci
Godsey, Jim
Mansinho, André
Macedo, Daniela
Lobo-Martins, Soraia
Filipe, Pedro
Esteves, Rui
Coutinho, João
Costa, Paulo Matos
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
Abreu, Catarina
Costa, Ana Lúcia
Zhang, Shile
Pawlowski, Traci
Godsey, Jim
Mansinho, André
Macedo, Daniela
Lobo-Martins, Soraia
Filipe, Pedro
Esteves, Rui
Coutinho, João
Costa, Paulo Matos
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 UCIBIO - Applied Molecular Biosciences Unit
DCV - Departamento de Ciências da Vida
RUN
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
Abreu, Catarina
Costa, Ana Lúcia
Zhang, Shile
Pawlowski, Traci
Godsey, Jim
Mansinho, André
Macedo, Daniela
Lobo-Martins, Soraia
Filipe, Pedro
Esteves, Rui
Coutinho, João
Costa, Paulo Matos
Ramires, Afonso
Aldeia, Fernando
Quintela, António
So, Alex
Liu, Li
Grosso, Ana Rita
Costa, Luis
dc.subject.por.fl_str_mv Colorectal Neoplasms/genetics
DNA Copy Number Variations
Humans
Oncogenes
Prospective Studies
Tumor Microenvironment/genetics
SDG 3 - Good Health and Well-being
topic Colorectal Neoplasms/genetics
DNA Copy Number Variations
Humans
Oncogenes
Prospective Studies
Tumor Microenvironment/genetics
SDG 3 - Good Health and Well-being
description We thank João Neto and remaining Computational Multi-Omics Lab members at UCIBIO for their helpful comments and suggestions. © 2022. The Author(s).
publishDate 2022
dc.date.none.fl_str_mv 2022-11-30T22:11:55Z
2022-09-09
2022-09-09T00:00:00Z
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/10362/145912
url http://hdl.handle.net/10362/145912
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PURE: 46643886
https://doi.org/10.1038/s42003-022-03884-x
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 14
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dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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