CORE
🇺🇦
make metadata, not war
Services
Services overview
Explore all CORE services
Access to raw data
API
Dataset
FastSync
Content discovery
Recommender
Discovery
OAI identifiers
OAI Resolver
Managing content
Dashboard
Bespoke contracts
Consultancy services
Support us
Support us
Membership
Sponsorship
Community governance
Advisory Board
Board of supporters
Research network
About
About us
Our mission
Team
Blog
FAQs
Contact us
Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development
Authors
Fernando Aldeia
Paula Borralho
+29 more
Sandra Casimiro
Ana Lúcia Costa
Luis Costa
Paulo M. Costa
Joao Coutinho
Rui Esteves
Afonso Fernandes
Cristina Ferreira
Pedro Filipe
Jim Godsey
Mahdi Golkaram
Ana Rita Grosso
Shannon Kaplan
Nafeesa Khan
Li Liu
Soraia Lobo-Martins
Daniela Macedo
André Mansinho
Catarina Marques
Marta Martins
Traci Pawlowski
Rui Pinto
António Quintela
Afonso Ramires
Michael Salmans
Alex So
Daniel Sobral
Raakhee Vijayaraghavan
Shile Zhang
Publication date
1 January 2022
Publisher
'Springer Science and Business Media LLC'
Doi
Cite
View
on
PubMed
Abstract
© 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.info:eu-repo/semantics/publishedVersio
Similar works
Full text
Open in the Core reader
Download PDF
Available Versions
PubMed Central
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:pubmedcentral.nih.gov:9463...
Last time updated on 06/11/2022
Universidade de Lisboa: Repositório.UL
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:repositorio.ul.pt:10451/54...
Last time updated on 06/10/2022
Repositório da Universidade Nova de Lisboa
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:run.unl.pt:10362/145912
Last time updated on 17/12/2022