TY  - JOUR
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
Y1  - 2017/05/02 
JF  - Genome Research 
JO  - Genome Research 
DO  - 10.1101/gr.214296.116 
UR  - http://genome.cshlp.org/content/early/2017/05/02/gr.214296.116.abstract 
N2  - 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. 
ER  -