The clonal evolution of metastatic colorectal cancer.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
07
08
2019
accepted:
10
04
2020
entrez:
25
6
2020
pubmed:
25
6
2020
medline:
9
4
2022
Statut:
epublish
Résumé
Tumor heterogeneity and evolution drive treatment resistance in metastatic colorectal cancer (mCRC). Patient-derived xenografts (PDXs) can model mCRC biology; however, their ability to accurately mimic human tumor heterogeneity is unclear. Current genomic studies in mCRC have limited scope and lack matched PDXs. Therefore, the landscape of tumor heterogeneity and its impact on the evolution of metastasis and PDXs remain undefined. We performed whole-genome, deep exome, and targeted validation sequencing of multiple primary regions, matched distant metastases, and PDXs from 11 patients with mCRC. We observed intricate clonal heterogeneity and evolution affecting metastasis dissemination and PDX clonal selection. Metastasis formation followed both monoclonal and polyclonal seeding models. In four cases, metastasis-seeding clones were not identified in any primary region, consistent with a metastasis-seeding-metastasis model. PDXs underrepresented the subclonal heterogeneity of parental tumors. These suggest that single sample tumor sequencing and current PDX models may be insufficient to guide precision medicine.
Identifiants
pubmed: 32577507
doi: 10.1126/sciadv.aay9691
pii: aay9691
pmc: PMC7286679
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
eaay9691Subventions
Organisme : NCI NIH HHS
ID : P30 CA091842
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA101937
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197561
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA223112
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK052574
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224083
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA185983
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009621
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197561
Pays : United States
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
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