@article{Noorani02052017, author = {Noorani, Ayesha and Bornschein, Jan and Lynch, Andy G. and Secrier, Maria and Achilleos, Achilleas and Eldridge, Matthew and Bower, Lawrence and Weaver, Jamie M.J. and Crawte, Jason and Ong, Chin-Ann and Shannon, Nicholas and MacRae, Shona and Grehan, Nicola and Nutzinger, Barbara and O'Donovan, Maria and Hardwick, Richard and Tavaré, Simon and Fitzgerald, Rebecca C. and on behalf of the Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium and Elliott, Rachael Fels and Edwards, Paul A.W. and Li, Xiaodun and Chettouh, Hamza and Contini, Gianmarco and Gregson, Eleanor and Zeki, Sebastian and Smith, Laura and Abdullahi, Zarah and de la Rue, Rachel and Miremadi, Ahmad and Malhotra, Shalini and Smith, Mike L. and Davies, Jim and Crichton, Charles and Carroll, Nick and Safranek, Peter and Hindmarsh, Andrew and Sujendran, Vijayendran and Turkington, Richard and Hayes, Stephen J. and Ang, Yeng and Preston, Shaun R. and Oakes, Sarah and Bagwan, Izhar and Save, Vicki and Skipworth, Richard J.E. and Hupp, Ted R. and O'Neill, J. Robert and Tucker, Olga and Beggs, Andrew and Taniere, Philippe and Underwood, Timothy J. and Noble, Fergus and Owsley, Jack and Barr, Hugh and Shepherd, Neil and Old, Oliver and Lagergren, Jesper and Gossage, James and Davies, Andrew and Chang, Fuju and Zylstra, Janine and Sanders, Grant and Berrisford, Richard and Harden, Catherine and Bunting, David and Lewis, Mike and Cheong, Ed and Kumar, Bhaskar and Parsons, Simon L. and Soomro, Irshad and Kaye, Philip and Lovat, Laurence and Haidry, Rehan and Eneh, Victor and Igali, Laszlo and Scott, Michael and Sothi, Shamila and Suortamo, Sari and Lishman, Suzy}, title = {A comparative analysis of whole genome sequencing of oesophageal adenocarcinoma pre- and post-chemotherapy}, year = {2017}, doi = {10.1101/gr.214296.116}, 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.}, URL = {http://genome.cshlp.org/content/early/2017/05/02/gr.214296.116.abstract}, eprint = {http://genome.cshlp.org/content/early/2017/05/02/gr.214296.116.full.pdf+html}, journal = {Genome Research} }