Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma.
Hardwick, Richard H
Stratton, Michael R
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Noorani, A., Li, X., Goddard, M., Crawte, J., Alexandrov, L. B., Secrier, M., Eldridge, M., et al. (2020). Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma.. Nature genetics, 52 (1), 74-83. https://doi.org/10.1038/s41588-019-0551-3
The poor outcomes in esophageal adenocarcinoma (EAC) prompted us to interrogate the 28 pattern and timing of metastatic spread. Whole genome sequencing and phylogenetic 29 analysis of 388 samples across 18 EAC cases demonstrated in 90% of cases that multiple 30 subclones from the primary tumor spread very rapidly from the primary site to form 31 multiple metastases, including lymph nodes and distant tissues, a mode of dissemination 32 that we term ‘clonal diaspora’. Metastatic subclones at autopsy were present in tissue and 33 blood samples from earlier time-points. These findings have implications for our 34 understanding and clinical evaluation of EAC
Humans, Adenocarcinoma, Esophageal Neoplasms, Models, Statistical, Genomics, Phylogeny, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Male, Young Adult, Clonal Evolution, Whole Genome Sequencing
MRC core grant (RG84369), an NIHR Research Professorship (RG67258) and Cancer Research UK (RG66287).
Medical Research Council (MC_UU_12022/2)
Cancer Research UK (15874)
Cancer Research UK (A12770)
External DOI: https://doi.org/10.1038/s41588-019-0551-3
This record's URL: https://www.repository.cam.ac.uk/handle/1810/299509
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