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Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Noorani, Ayesha 
Li, Xiaodun 
Goddard, Martin 
Crawte, Jason 
Alexandrov, Ludmil B  ORCID logo  https://orcid.org/0000-0003-3596-4515

Abstract

The poor outcomes in esophageal adenocarcinoma (EAC) prompted us to interrogate the pattern and timing of metastatic spread. Whole-genome sequencing and phylogenetic analysis of 388 samples across 18 individuals with EAC showed, in 90% of patients, that multiple subclones from the primary tumor spread very rapidly from the primary site to form multiple metastases, including lymph nodes and distant tissues-a mode of dissemination that we term 'clonal diaspora'. Metastatic subclones at autopsy were present in tissue and blood samples from earlier time points. These findings have implications for our understanding and clinical evaluation of EAC.

Description

Keywords

Adenocarcinoma, Adolescent, Adult, Aged, Aged, 80 and over, Child, Clonal Evolution, Esophageal Neoplasms, Genomics, Humans, Male, Middle Aged, Models, Statistical, Phylogeny, Whole Genome Sequencing, Young Adult

Journal Title

Nat Genet

Conference Name

Journal ISSN

1061-4036
1546-1718

Volume Title

52

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Medical Research Council (MC_UU_12022/2)
Cancer Research Uk (None)
Medical Research Council (MC_EX_UU_MR/K00316X/1)
Cancer Research Uk (None)
TCC (None)
National Cancer Institute (P30CA023100)
Cancer Research UK (22720)
Cancer Research UK (22131)
MRC core grant (RG84369), an NIHR Research Professorship (RG67258) and Cancer Research UK (RG66287).