Obulkasim, A;
Ylstra, B;
van Essen, HF;
Benner, C;
Stenning, S;
Langley, R;
Allum, W;
... Grabsch, HI; + view all
(2016)
Reduced genomic tumor heterogeneity after neoadjuvant chemotherapy is related to favorable outcome in patients with esophageal adenocarcinoma.
Oncotarget
, 7
(28)
pp. 44084-44095.
10.18632/oncotarget.9857.
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Abstract
Neoadjuvant chemo(radio)therapy followed by surgery is the standard of care for patients with locally advanced resectable esophageal adenocarcinoma (EAC). There is increasing evidence that drug resistance might be related to genomic heterogeneity. We investigated whether genomic tumor heterogeneity is different after cytotoxic chemotherapy and is associated with EAC patient survival. We used arrayCGH and a quantitative assessment of the whole genome DNA copy number aberration patterns ('DNA copy number entropy') to establish the level of genomic tumor heterogeneity in 80 EAC treated with neoadjuvant chemotherapy followed by surgery (CS group) or surgery alone (S group). The association between DNA copy number entropy, clinicopathological variables and survival was investigated.DNA copy number entropy was reduced after chemotherapy, even if there was no morphological evidence of response to therapy (p<0.001). Low DNA copy number entropy was associated with improved survival in the CS group (p=0.011) but not in the S group (p=0.396).Our results suggest that cytotoxic chemotherapy reduces DNA copy number entropy, which might be a more sensitive tumor response marker than changes in the morphological tumor phenotype. The use of DNA copy number entropy in clinical practice will require validation of our results in a prospective study.
| Type: | Article |
|---|---|
| Title: | Reduced genomic tumor heterogeneity after neoadjuvant chemotherapy is related to favorable outcome in patients with esophageal adenocarcinoma |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.18632/oncotarget.9857 |
| Publisher version: | http://dx.doi.org/10.18632/oncotarget.9857 |
| Language: | English |
| Additional information: | Copyright © 2016 Impact Journals, LLC. All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License (CC BY 3.0) (https://creativecommons.org/licenses/by/3.0/) |
| Keywords: | array CGH, chemotherapy, esophageal adenocarcinoma, prognosis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1499898 |
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