Reduced genomic tumor heterogeneity after neoadjuvant chemotherapy is related to favorable outcome in patients with esophageal adenocarcinoma

Askar Obulkasim; Bauke Ylstra; Hendrik F. van Essen; Christian Benner; Sally Stenning; Ruth Langley; William Allum; David Cunningham; Imran Inam; Lindsay C. Hewitt; Nicolas P. West; Gerrit A. Meijer; Mark A. van de Wiel; Heike I. Grabsch

doi:10.18632/oncotarget.9857

Reduced genomic tumor heterogeneity after neoadjuvant chemotherapy is related to favorable outcome in patients with esophageal adenocarcinoma

Askar Obulkasim, Bauke Ylstra, Hendrik F. van Essen, Christian Benner, Sally Stenning, Ruth Langley, William Allum, David Cunningham, Imran Inam, Lindsay C. Hewitt, Nicolas P. West, Gerrit A. Meijer, Mark A. van de Wiel, Heike I. Grabsch^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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

Original language	English
Pages (from-to)	44084-44095
Number of pages	12
Journal	Oncotarget
Volume	7
Issue number	28
DOIs	https://doi.org/10.18632/oncotarget.9857
Publication status	Published - 12 Jul 2016

Keywords

esophageal adenocarcinoma
array CGH
prognosis
chemotherapy

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10.18632/oncotarget.9857Licence: CC BY

Cite this

Obulkasim, A., Ylstra, B., van Essen, H. F., Benner, C., Stenning, S., Langley, R., Allum, W., Cunningham, D., Inam, I., Hewitt, L. C., West, N. P., Meijer, G. A., van de Wiel, M. A., & Grabsch, H. I. (2016). Reduced genomic tumor heterogeneity after neoadjuvant chemotherapy is related to favorable outcome in patients with esophageal adenocarcinoma. Oncotarget, 7(28), 44084-44095. https://doi.org/10.18632/oncotarget.9857

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title = "Reduced genomic tumor heterogeneity after neoadjuvant chemotherapy is related to favorable outcome in patients with esophageal adenocarcinoma",

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",

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Obulkasim, A, Ylstra, B, van Essen, HF, Benner, C, Stenning, S, Langley, R, Allum, W, Cunningham, D, Inam, I, Hewitt, LC, West, NP, Meijer, GA, van de Wiel, MA & Grabsch, HI 2016, 'Reduced genomic tumor heterogeneity after neoadjuvant chemotherapy is related to favorable outcome in patients with esophageal adenocarcinoma', Oncotarget, vol. 7, no. 28, pp. 44084-44095. https://doi.org/10.18632/oncotarget.9857

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AU - Obulkasim, Askar

AU - Ylstra, Bauke

AU - van Essen, Hendrik F.

AU - Benner, Christian

AU - Stenning, Sally

AU - Langley, Ruth

AU - Allum, William

AU - Cunningham, David

AU - Inam, Imran

AU - Hewitt, Lindsay C.

AU - West, Nicolas P.

AU - Meijer, Gerrit A.

AU - van de Wiel, Mark A.

AU - Grabsch, Heike I.

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N2 - 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

AB - 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

KW - esophageal adenocarcinoma

KW - array CGH

KW - prognosis

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