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

A. Noorani; X. Li; M. Goddard; J. Crawte; L.B. Alexandrov; M. Secrier; M.D. Eldridge; L. Bower; J. Weaver; P. Lao-Sirieix; I. Martincorena; I. Debiram-Beecham; N. Grehan; S. MacRae; S. Malhotra; A. Miremadi; T. Thomas; S. Galbraith; L. Petersen; S.D. Preston; D. Gilligan; A. Hindmarsh; R.H. Hardwick; M.R. Stratton; D.C. Wedge; R.C. Fitzgerald

doi:10.1038/s41588-019-0551-3

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

A. Noorani, X. Li, M. Goddard, J. Crawte, L.B. Alexandrov, M. Secrier, M.D. Eldridge, L. Bower, J. Weaver, P. Lao-Sirieix, I. Martincorena, I. Debiram-Beecham, N. Grehan, S. MacRae, S. Malhotra, A. Miremadi, T. Thomas, S. Galbraith, L. Petersen, S.D. PrestonD. Gilligan, A. Hindmarsh, R.H. Hardwick, M.R. Stratton, D.C. Wedge, R.C. Fitzgerald

Division of Cancer Sciences (L5)

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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.

Original language	Undefined
Journal	Nature Genetics
Early online date	6 Jan 2020
DOIs	https://doi.org/10.1038/s41588-019-0551-3
Publication status	Published - 6 Jan 2020

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41588-019-0551-3

Noorani20Accepted author manuscript, 9.79 MB

Cite this

Noorani, A., Li, X., Goddard, M., Crawte, J., Alexandrov, L. B., Secrier, M., Eldridge, M. D., Bower, L., Weaver, J., Lao-Sirieix, P., Martincorena, I., Debiram-Beecham, I., Grehan, N., MacRae, S., Malhotra, S., Miremadi, A., Thomas, T., Galbraith, S., Petersen, L., ... Fitzgerald, R. C. (2020). Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma. Nature Genetics. https://doi.org/10.1038/s41588-019-0551-3

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title = "Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma",

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 {\textquoteleft}clonal diaspora{\textquoteright}. 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.",

author = "A. Noorani and X. Li and M. Goddard and J. Crawte and L.B. Alexandrov and M. Secrier and M.D. Eldridge and L. Bower and J. Weaver and P. Lao-Sirieix and I. Martincorena and I. Debiram-Beecham and N. Grehan and S. MacRae and S. Malhotra and A. Miremadi and T. Thomas and S. Galbraith and L. Petersen and S.D. Preston and D. Gilligan and A. Hindmarsh and R.H. Hardwick and M.R. Stratton and D.C. Wedge and R.C. Fitzgerald",

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Noorani, A, Li, X, Goddard, M, Crawte, J, Alexandrov, LB, Secrier, M, Eldridge, MD, Bower, L, Weaver, J, Lao-Sirieix, P, Martincorena, I, Debiram-Beecham, I, Grehan, N, MacRae, S, Malhotra, S, Miremadi, A, Thomas, T, Galbraith, S, Petersen, L, Preston, SD, Gilligan, D, Hindmarsh, A, Hardwick, RH, Stratton, MR, Wedge, DC & Fitzgerald, RC 2020, 'Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma', Nature Genetics. https://doi.org/10.1038/s41588-019-0551-3

TY - JOUR

T1 - Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma

AU - Noorani, A.

AU - Li, X.

AU - Goddard, M.

AU - Crawte, J.

AU - Alexandrov, L.B.

AU - Secrier, M.

AU - Eldridge, M.D.

AU - Bower, L.

AU - Weaver, J.

AU - Lao-Sirieix, P.

AU - Martincorena, I.

AU - Debiram-Beecham, I.

AU - Grehan, N.

AU - MacRae, S.

AU - Malhotra, S.

AU - Miremadi, A.

AU - Thomas, T.

AU - Galbraith, S.

AU - Petersen, L.

AU - Preston, S.D.

AU - Gilligan, D.

AU - Hindmarsh, A.

AU - Hardwick, R.H.

AU - Stratton, M.R.

AU - Wedge, D.C.

AU - Fitzgerald, R.C.

PY - 2020/1/6

Y1 - 2020/1/6

N2 - 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.

AB - 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.

U2 - 10.1038/s41588-019-0551-3

DO - 10.1038/s41588-019-0551-3

M3 - Article

SN - 1061-4036

JO - Nature Genetics

JF - Nature Genetics

ER -