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A comparative analysis of whole genome sequencing of oesophageal adenocarcinoma pre- and post-chemotherapy

A comparative analysis of whole genome sequencing of oesophageal adenocarcinoma pre- and post-chemotherapy
A comparative analysis of whole genome sequencing of oesophageal adenocarcinoma pre- and post-chemotherapy

The scientific community has avoided using tissue samples from patients that have been exposed to systemic chemotherapy to infer the genomic landscape of a given cancer. Esophageal adenocarcinoma is a heterogeneous, chemoresistant tumor for which the availability and size of pretreatment endoscopic samples are limiting. This study compares whole-genome sequencing data obtained from chemo-naive and chemo-treated samples. The quality of whole-genomic sequencing data is comparable across all samples regardless of chemotherapy status. Inclusion of samples collected post-chemotherapy increased the proportion of late-stage tumors. When comparing matched pre- and post-chemotherapy samples from 10 cases, the mutational signatures, copy number, and SNV mutational profiles reflect the expected heterogeneity in this disease. Analysis of SNVs in relation to allele-specific copy-number changes pinpoints the common ancestor to a point prior to chemotherapy. For cases in which pre- and post-chemotherapy samples do show substantial differences, the timing of the divergence is near-synchronous with endoreduplication. Comparison across a large prospective cohort (62 treatment-naive, 58 chemotherapy-treated samples) reveals no significant differences in the overall mutation rate, mutation signatures, specific recurrent point mutations, or copy-number events in respect to chemotherapy status. In conclusion, whole-genome sequencing of samples obtained following neoadjuvant chemotherapy is representative of the genomic landscape of esophageal adenocarcinoma. Excluding these samples reduces the material available for cataloging and introduces a bias toward the earlier stages of cancer.

Journal Article
1088-9051
902-912
Noorani, Ayesha
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Bornschein, Jan
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Lynch, Andy G.
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Secrier, Maria
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Achilleos, Achilleas
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Eldridge, Matthew
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Bower, Lawrence
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Weaver, Jamie M.J.
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Crawte, Jason
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Ong, Chin-Ann
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Shannon, Nicholas
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MacRae, Shona
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Grehan, Nicola
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Nutzinger, Barbara
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O'Donovan, Maria
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Hardwick, Richard
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Tavaré, Simon
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Fitzgerald, Rebecca C
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Elliott, Rachael Fels
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Edwards, Paul A W
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Li, Xiaodun
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Chettouh, Hamza
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Contini, Gianmarco
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Gregson, Eleanor
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Zeki, Sebastian
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Smith, Laura
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Abdullahi, Zarah
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de la Rue, Rachel
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Miremadi, Ahmad
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Malhotra, Shalini
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Smith, Mike L
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Davies, Jim
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Crichton, Charles
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Carroll, Nick
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Safranek, Peter
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Hindmarsh, Andrew
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Sujendran, Vijayendran
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Turkington, Richard
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Hayes, Stephen J
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Ang, Yeng
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Preston, Shaun R
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Oakes, Sarah
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Bagwan, Izhar
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Save, Vicki
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Skipworth, Richard J E
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Hupp, Ted R
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O'Neill, J Robert
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Tucker, Olga
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Underwood, Timothy J
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Noble, Fergus
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Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium
Noorani, Ayesha
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Bornschein, Jan
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Lynch, Andy G.
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Secrier, Maria
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Achilleos, Achilleas
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Eldridge, Matthew
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Bower, Lawrence
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Weaver, Jamie M.J.
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Crawte, Jason
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Ong, Chin-Ann
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Shannon, Nicholas
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MacRae, Shona
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Grehan, Nicola
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Nutzinger, Barbara
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O'Donovan, Maria
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Hardwick, Richard
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Tavaré, Simon
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Fitzgerald, Rebecca C
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Elliott, Rachael Fels
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Edwards, Paul A W
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Li, Xiaodun
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Chettouh, Hamza
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Contini, Gianmarco
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Gregson, Eleanor
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Zeki, Sebastian
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Smith, Laura
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Abdullahi, Zarah
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de la Rue, Rachel
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Miremadi, Ahmad
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Malhotra, Shalini
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Smith, Mike L
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Davies, Jim
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Crichton, Charles
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Carroll, Nick
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Safranek, Peter
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Hindmarsh, Andrew
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Sujendran, Vijayendran
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Turkington, Richard
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Hayes, Stephen J
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Ang, Yeng
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Preston, Shaun R
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Oakes, Sarah
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Bagwan, Izhar
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Save, Vicki
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Skipworth, Richard J E
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Hupp, Ted R
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O'Neill, J Robert
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Tucker, Olga
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Underwood, Timothy J
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Noble, Fergus
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Noorani, Ayesha, Bornschein, Jan, Lynch, Andy G., Secrier, Maria, Achilleos, Achilleas, Eldridge, Matthew, Bower, Lawrence, Weaver, Jamie M.J., Crawte, Jason, Ong, Chin-Ann, Shannon, Nicholas, MacRae, Shona, Grehan, Nicola, Nutzinger, Barbara, O'Donovan, Maria, Hardwick, Richard, Tavaré, Simon and Fitzgerald, Rebecca C , Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium (2017) A comparative analysis of whole genome sequencing of oesophageal adenocarcinoma pre- and post-chemotherapy. Genome Research, 27, 902-912. (doi:10.1101/gr.214296.116).

Record type: Article

Abstract

The scientific community has avoided using tissue samples from patients that have been exposed to systemic chemotherapy to infer the genomic landscape of a given cancer. Esophageal adenocarcinoma is a heterogeneous, chemoresistant tumor for which the availability and size of pretreatment endoscopic samples are limiting. This study compares whole-genome sequencing data obtained from chemo-naive and chemo-treated samples. The quality of whole-genomic sequencing data is comparable across all samples regardless of chemotherapy status. Inclusion of samples collected post-chemotherapy increased the proportion of late-stage tumors. When comparing matched pre- and post-chemotherapy samples from 10 cases, the mutational signatures, copy number, and SNV mutational profiles reflect the expected heterogeneity in this disease. Analysis of SNVs in relation to allele-specific copy-number changes pinpoints the common ancestor to a point prior to chemotherapy. For cases in which pre- and post-chemotherapy samples do show substantial differences, the timing of the divergence is near-synchronous with endoreduplication. Comparison across a large prospective cohort (62 treatment-naive, 58 chemotherapy-treated samples) reveals no significant differences in the overall mutation rate, mutation signatures, specific recurrent point mutations, or copy-number events in respect to chemotherapy status. In conclusion, whole-genome sequencing of samples obtained following neoadjuvant chemotherapy is representative of the genomic landscape of esophageal adenocarcinoma. Excluding these samples reduces the material available for cataloging and introduces a bias toward the earlier stages of cancer.

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GENOME_2016-214296_final - Accepted Manuscript
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Genome Res.-2017-Noorani-902-12 - Version of Record
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Accepted/In Press date: 6 April 2017
e-pub ahead of print date: 2 May 2017
Published date: June 2017
Keywords: Journal Article

Identifiers

Local EPrints ID: 413231
URI: http://eprints.soton.ac.uk/id/eprint/413231
ISSN: 1088-9051
PURE UUID: cb2faac8-2f1c-4f52-834c-9494ada96cec
ORCID for Timothy J Underwood: ORCID iD orcid.org/0000-0001-9455-2188

Catalogue record

Date deposited: 17 Aug 2017 16:31
Last modified: 16 Mar 2024 03:35

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Contributors

Author: Ayesha Noorani
Author: Jan Bornschein
Author: Andy G. Lynch
Author: Maria Secrier
Author: Achilleas Achilleos
Author: Matthew Eldridge
Author: Lawrence Bower
Author: Jamie M.J. Weaver
Author: Jason Crawte
Author: Chin-Ann Ong
Author: Nicholas Shannon
Author: Shona MacRae
Author: Nicola Grehan
Author: Barbara Nutzinger
Author: Maria O'Donovan
Author: Richard Hardwick
Author: Simon Tavaré
Author: Rebecca C Fitzgerald
Author: Rachael Fels Elliott
Author: Paul A W Edwards
Author: Xiaodun Li
Author: Hamza Chettouh
Author: Gianmarco Contini
Author: Eleanor Gregson
Author: Sebastian Zeki
Author: Laura Smith
Author: Zarah Abdullahi
Author: Rachel de la Rue
Author: Ahmad Miremadi
Author: Shalini Malhotra
Author: Mike L Smith
Author: Jim Davies
Author: Charles Crichton
Author: Nick Carroll
Author: Peter Safranek
Author: Andrew Hindmarsh
Author: Vijayendran Sujendran
Author: Richard Turkington
Author: Stephen J Hayes
Author: Yeng Ang
Author: Shaun R Preston
Author: Sarah Oakes
Author: Izhar Bagwan
Author: Vicki Save
Author: Richard J E Skipworth
Author: Ted R Hupp
Author: J Robert O'Neill
Author: Olga Tucker
Author: Fergus Noble
Corporate Author: Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium

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