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Whole genome methylation analysis of nondysplastic barrett esophagus that progresses to invasive cancer

Whole genome methylation analysis of nondysplastic barrett esophagus that progresses to invasive cancer
Whole genome methylation analysis of nondysplastic barrett esophagus that progresses to invasive cancer

OBJECTIVE: To investigate differences in methylation between patients with nondysplastic Barrett esophagus who progress to invasive adenocarcinoma and those who do not.

BACKGROUND: Identifying patients with nondysplastic Barrett esophagus who progress to invasive adenocarcinoma remains a challenge. Previous studies have demonstrated the potential utility of epigenetic markers for identifying this group.

METHODS: A whole genome methylation interrogation using the Illumina HumanMethylation 450 array of patients with nondysplastic Barrett esophagus who either develop adenocarcinoma or remain static, with validation of findings by bisulfite pyrosequencing.

RESULTS: In all, 12 patients with "progressive" versus 12 with "nonprogressive" nondysplastic Barrett esophagus were analyzed via methylation array. Forty-four methylation markers were identified that may be able to discriminate between nondysplastic Barrett esophagus that either progress to adenocarcinoma or remain static. Hypomethylation of the recently identified tumor suppressor OR3A4 (probe cg09890332) validated in a separate cohort of samples (median methylation in progressors 67.8% vs 96.7% in nonprogressors; P = 0.0001, z = 3.85, Wilcoxon rank-sum test) and was associated with the progression to adenocarcinoma. There were no differences in copy number between the 2 groups, but a global trend towards hypomethylation in the progressor group was observed.

CONCLUSION: Hypomethylation of OR3A4 has the ability to risk stratify the patient with nondysplastic Barrett esophagus and may form the basis of a future surveillance program.

Journal Article
0003-4932
479–485
Dilworth, Mark P.
6895741f-1ea5-4f51-ac89-fb14841ecb1f
Nieto, Tom
bcb142d0-7c0b-4402-b983-e82df50506c0
Stockton, Jo D.
53db4e22-8aa0-4e04-ae3b-c7bb782fad60
Whalley, Celina M.
64c2a23b-31f6-437e-be9c-d1668edee99b
Tee, Louise
b7ec4490-323a-45a8-99cc-c915c6c1a33a
James, Jonathan D.
c2dca568-0b4f-4376-b005-2bc551cef2b1
Underwood, Timothy
8e81bf60-edd2-4b0e-8324-3068c95ea1c6
Noble, Fergus
4f14574c-28f2-4e04-bd95-f53c7649e1fa
Hallissey, Michael T.
27e98250-6995-4655-bdfc-55b988f109ea
Hejmadi, Rahul
919272ce-08fe-4983-b300-25229dab8b1e
Trudgill, Nigel
f48d748a-c06f-4fd5-929a-6403784976f4
Tucker, Olga
feb4ecbc-b46e-43ac-a146-e777472e788e
Beggs, Andrew D.
fe399221-77bc-4be2-b45e-739e1d889581
Dilworth, Mark P.
6895741f-1ea5-4f51-ac89-fb14841ecb1f
Nieto, Tom
bcb142d0-7c0b-4402-b983-e82df50506c0
Stockton, Jo D.
53db4e22-8aa0-4e04-ae3b-c7bb782fad60
Whalley, Celina M.
64c2a23b-31f6-437e-be9c-d1668edee99b
Tee, Louise
b7ec4490-323a-45a8-99cc-c915c6c1a33a
James, Jonathan D.
c2dca568-0b4f-4376-b005-2bc551cef2b1
Underwood, Timothy
8e81bf60-edd2-4b0e-8324-3068c95ea1c6
Noble, Fergus
4f14574c-28f2-4e04-bd95-f53c7649e1fa
Hallissey, Michael T.
27e98250-6995-4655-bdfc-55b988f109ea
Hejmadi, Rahul
919272ce-08fe-4983-b300-25229dab8b1e
Trudgill, Nigel
f48d748a-c06f-4fd5-929a-6403784976f4
Tucker, Olga
feb4ecbc-b46e-43ac-a146-e777472e788e
Beggs, Andrew D.
fe399221-77bc-4be2-b45e-739e1d889581

Dilworth, Mark P., Nieto, Tom, Stockton, Jo D., Whalley, Celina M., Tee, Louise, James, Jonathan D., Underwood, Timothy, Noble, Fergus, Hallissey, Michael T., Hejmadi, Rahul, Trudgill, Nigel, Tucker, Olga and Beggs, Andrew D. (2019) Whole genome methylation analysis of nondysplastic barrett esophagus that progresses to invasive cancer. Annals of Surgery, 269 (3), 479–485. (doi:10.1097/SLA.0000000000002658).

Record type: Article

Abstract

OBJECTIVE: To investigate differences in methylation between patients with nondysplastic Barrett esophagus who progress to invasive adenocarcinoma and those who do not.

BACKGROUND: Identifying patients with nondysplastic Barrett esophagus who progress to invasive adenocarcinoma remains a challenge. Previous studies have demonstrated the potential utility of epigenetic markers for identifying this group.

METHODS: A whole genome methylation interrogation using the Illumina HumanMethylation 450 array of patients with nondysplastic Barrett esophagus who either develop adenocarcinoma or remain static, with validation of findings by bisulfite pyrosequencing.

RESULTS: In all, 12 patients with "progressive" versus 12 with "nonprogressive" nondysplastic Barrett esophagus were analyzed via methylation array. Forty-four methylation markers were identified that may be able to discriminate between nondysplastic Barrett esophagus that either progress to adenocarcinoma or remain static. Hypomethylation of the recently identified tumor suppressor OR3A4 (probe cg09890332) validated in a separate cohort of samples (median methylation in progressors 67.8% vs 96.7% in nonprogressors; P = 0.0001, z = 3.85, Wilcoxon rank-sum test) and was associated with the progression to adenocarcinoma. There were no differences in copy number between the 2 groups, but a global trend towards hypomethylation in the progressor group was observed.

CONCLUSION: Hypomethylation of OR3A4 has the ability to risk stratify the patient with nondysplastic Barrett esophagus and may form the basis of a future surveillance program.

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or3a4 paper v7 for AnnSurg with corrections v2 - Accepted Manuscript
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More information

e-pub ahead of print date: 30 January 2018
Published date: March 2019
Keywords: Journal Article

Identifiers

Local EPrints ID: 418566
URI: https://eprints.soton.ac.uk/id/eprint/418566
ISSN: 0003-4932
PURE UUID: 906696d7-3bb1-47f0-8de5-0933b8477114
ORCID for Timothy Underwood: ORCID iD orcid.org/0000-0001-9455-2188

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Date deposited: 12 Mar 2018 17:30
Last modified: 10 Dec 2019 05:30

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