RT Journal
A1 Noorani, Ayesha
A1 Bornschein, Jan
A1 Lynch, Andy G.
A1 Secrier, Maria
A1 Achilleos, Achilleas
A1 Eldridge, Matthew
A1 Bower, Lawrence
A1 Weaver, Jamie M.J.
A1 Crawte, Jason
A1 Ong, Chin-Ann
A1 Shannon, Nicholas
A1 MacRae, Shona
A1 Grehan, Nicola
A1 Nutzinger, Barbara
A1 O'Donovan, Maria
A1 Hardwick, Richard
A1 Tavaré, Simon
A1 Fitzgerald, Rebecca C.
A1 on behalf of the Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium
A1 Elliott, Rachael Fels
A1 Edwards, Paul A.W.
A1 Li, Xiaodun
A1 Chettouh, Hamza
A1 Contini, Gianmarco
A1 Gregson, Eleanor
A1 Zeki, Sebastian
A1 Smith, Laura
A1 Abdullahi, Zarah
A1 de la Rue, Rachel
A1 Miremadi, Ahmad
A1 Malhotra, Shalini
A1 Smith, Mike L.
A1 Davies, Jim
A1 Crichton, Charles
A1 Carroll, Nick
A1 Safranek, Peter
A1 Hindmarsh, Andrew
A1 Sujendran, Vijayendran
A1 Turkington, Richard
A1 Hayes, Stephen J.
A1 Ang, Yeng
A1 Preston, Shaun R.
A1 Oakes, Sarah
A1 Bagwan, Izhar
A1 Save, Vicki
A1 Skipworth, Richard J.E.
A1 Hupp, Ted R.
A1 O'Neill, J. Robert
A1 Tucker, Olga
A1 Beggs, Andrew
A1 Taniere, Philippe
A1 Underwood, Timothy J.
A1 Noble, Fergus
A1 Owsley, Jack
A1 Barr, Hugh
A1 Shepherd, Neil
A1 Old, Oliver
A1 Lagergren, Jesper
A1 Gossage, James
A1 Davies, Andrew
A1 Chang, Fuju
A1 Zylstra, Janine
A1 Sanders, Grant
A1 Berrisford, Richard
A1 Harden, Catherine
A1 Bunting, David
A1 Lewis, Mike
A1 Cheong, Ed
A1 Kumar, Bhaskar
A1 Parsons, Simon L.
A1 Soomro, Irshad
A1 Kaye, Philip
A1 Lovat, Laurence
A1 Haidry, Rehan
A1 Eneh, Victor
A1 Igali, Laszlo
A1 Scott, Michael
A1 Sothi, Shamila
A1 Suortamo, Sari
A1 Lishman, Suzy
T1 A comparative analysis of whole genome sequencing of oesophageal adenocarcinoma pre- and post-chemotherapy
JF Genome Research 
JO Genome Research 
YR 2017 
FD May 02 
DO 10.1101/gr.214296.116 
UL http://genome.cshlp.org/content/early/2017/05/02/gr.214296.116.abstract 
AB 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.