Please use this identifier to cite or link to this item: https://doi.org/10.1101/gr.214296.116
Title: A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre-and post-chemotherapy
Authors: Noorani, 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
Keywords: trinucleotide
antineoplastic agent
tumor protein
adult
aged
Article
cancer chemotherapy
cancer staging
cohort analysis
comparative study
controlled clinical trial
controlled study
endoreduplication
esophageal adenocarcinoma
female
gene dosage
gene mutation
human
major clinical study
male
priority journal
prospective study
quality control
whole genome sequencing
adenocarcinoma
biology
cell transformation
copy number variation
esophagus
esophagus tumor
gene expression profiling
gene expression regulation
genetics
high throughput sequencing
human genome
metabolism
middle aged
mutation rate
neoadjuvant therapy
pathology
point mutation
procedures
single nucleotide polymorphism
time factor
Adenocarcinoma
Aged
Antineoplastic Agents
Cell Transformation, Neoplastic
Computational Biology
DNA Copy Number Variations
Esophageal Neoplasms
Esophagus
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genome, Human
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mutation Rate
Neoadjuvant Therapy
Neoplasm Proteins
Point Mutation
Polymorphism, Single Nucleotide
Prospective Studies
Time Factors
Issue Date: 2017
Publisher: Cold Spring Harbor Laboratory Press
Citation: Noorani, 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 (2017). A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre-and post-chemotherapy. Genome Research 27 (6) : 902-912. ScholarBank@NUS Repository. https://doi.org/10.1101/gr.214296.116
Rights: Attribution 4.0 International
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. © 2017 Tranchevent et al.
Source Title: Genome Research
URI: https://scholarbank.nus.edu.sg/handle/10635/179199
ISSN: 10889051
DOI: 10.1101/gr.214296.116
Rights: Attribution 4.0 International
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