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
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
June 2017
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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