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A comparative analy...
A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapy
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Noorani, A (author)
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Bornschein, J (author)
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Lynch, AG (author)
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Secrier, M (author)
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Achilleos, A (author)
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Eldridge, M (author)
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Bower, L (author)
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Weaver, JMJ (author)
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Crawte, J (author)
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Ong, CA (author)
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Shannon, N (author)
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MacRae, S (author)
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Grehan, N (author)
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Nutzinger, B (author)
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O'Donovan, M (author)
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Hardwick, R (author)
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Tavare, S (author)
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Fitzgerald, RC (author)
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- 2017-05-02
- 2017
- English.
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In: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 27:6, s. 902-912
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http://genome.cshlp....
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- 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.
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Noorani, A
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Bornschein, J
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Lynch, AG
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Secrier, M
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Achilleos, A
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Eldridge, M
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show more...
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Bower, L
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Weaver, JMJ
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Crawte, J
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Ong, CA
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Shannon, N
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MacRae, S
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Grehan, N
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Nutzinger, B
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O'Donovan, M
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Hardwick, R
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Tavare, S
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Fitzgerald, RC
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show less...
- Articles in the publication
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Genome research
- By the university
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Karolinska Institutet