Authors:
A Noorani, J Bornschein, AG Lynch, M Secrier, A Achilleos, M Eldridge, L Bower, JMJ Weaver, J Crawte, C-A Ong, N Shannon, S MacRae, N Grehan, B Nutzinger, M O'Donovan, R Hardwick, S Tavaré, RC Fitzgerald, Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium
Journal name: 
Genome Res
Citation info: 
27(6):902-912
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.
DOI: 
http://doi.org/10.1101/gr.214296.116
Research group: 
Tavaré Group
E-pub date: 
01 Jun 2017