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dc.contributor.authorNoorani, Ayesha
dc.contributor.authorBornschein, Jan
dc.contributor.authorLynch, Andy G
dc.contributor.authorSecrier, Maria
dc.contributor.authorAchilleos, Achilleas
dc.contributor.authorEldridge, Matthew
dc.contributor.authorBower, Lawrence
dc.contributor.authorWeaver, Jamie M.J.
dc.contributor.authorCrawte, Jason
dc.contributor.authorOng, Chin-Ann
dc.contributor.authorShannon, Nicholas
dc.contributor.authorMacRae, Shona
dc.contributor.authorGrehan, Nicola
dc.contributor.authorNutzinger, Barbara
dc.contributor.authorO'Donovan, Maria
dc.contributor.authorHardwick, Richard
dc.contributor.authorTavaré, Simon
dc.contributor.authorFitzgerald, Rebecca C.
dc.contributor.authorOesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium
dc.date.accessioned2017-08-11T14:30:10Z
dc.date.available2017-08-11T14:30:10Z
dc.date.issued2017-06-01
dc.identifier.citationNoorani , A , Bornschein , J , Lynch , A G , Secrier , M , Achilleos , A , Eldridge , M , Bower , L , Weaver , J M J , Crawte , J , Ong , C-A , Shannon , N , MacRae , S , Grehan , N , Nutzinger , B , O'Donovan , M , Hardwick , R , Tavaré , S , Fitzgerald , R C & Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium 2017 , ' A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapy ' , Genome Research , vol. 27 , no. 6 , pp. 902-912 . https://doi.org/10.1101/gr.214296.116en
dc.identifier.issn1088-9051
dc.identifier.otherPURE: 250731829
dc.identifier.otherPURE UUID: e286a118-d797-4221-957b-4b6157d3554e
dc.identifier.otherRIS: urn:3298CF335ADC48C31EA2EC5125C646BE
dc.identifier.otherScopus: 85020292652
dc.identifier.otherORCID: /0000-0002-7876-7338/work/35946867
dc.identifier.urihttps://hdl.handle.net/10023/11433
dc.descriptionThe whole-genome sequencing data from this study have been submitted to the European Genome-phenome Archive (EGA; https://www.ebi.ac.uk/ega/home) under accession number EGAD00001002241. Mutation calls can be found within the ICGC data portal (https://dcc.icgc.org/) under project ID ESADUK and library IDs listed in Supplemental Table S2.en
dc.description.abstractThe 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.
dc.format.extent11
dc.language.isoeng
dc.relation.ispartofGenome Researchen
dc.rights© 2017 Noorani et al. This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.en
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectDASen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.subject.lccRC0254en
dc.titleA comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapyen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Statisticsen
dc.contributor.institutionUniversity of St Andrews. Cellular Medicine Divisionen
dc.identifier.doihttps://doi.org/10.1101/gr.214296.116
dc.description.statusPeer revieweden


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