Subtypes of Barrett's oesophagus and oesophageal adenocarcinoma based on genome-wide methylation analysis.
Adenocarcinoma
/ drug therapy
Antineoplastic Agents
/ pharmacology
Barrett Esophagus
/ drug therapy
Cell Line, Tumor
Cell Movement
/ genetics
Cell Proliferation
/ genetics
DNA Methylation
DNA, Neoplasm
/ genetics
ErbB Receptors
/ metabolism
Esophageal Neoplasms
/ drug therapy
Gene Expression Regulation, Neoplastic
Gene Silencing
Genome-Wide Association Study
/ methods
Humans
Mutation
Neoplastic Stem Cells
/ metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 13
/ antagonists & inhibitors
Receptor, ErbB-2
/ metabolism
Signal Transduction
/ genetics
dysplasia
gastrointestinal cancer
methylation
Journal
Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
23
05
2017
revised:
06
04
2018
accepted:
22
04
2018
pubmed:
10
6
2018
medline:
14
7
2020
entrez:
10
6
2018
Statut:
ppublish
Résumé
To identify and characterise DNA methylation subtypes in oesophageal adenocarcinoma (EAC) and its precursor Barrett's oesophagus (BE). We performed genome-wide DNA methylation profiling on samples of non-dysplastic BE from cancer-free patients (n=59), EAC (n=23), normal squamous oesophagus (n=33) and normal fundus (n=9), and identified methylation subtypes using a recursively partitioned mixture model. We assessed genomic alterations for 9 BE and 22 EAC samples with massively parallel sequencing of 243 EAC-associated genes, and we conducted integrative analyses with transcriptome data to identify epigenetically repressed genes. We also carried out in vitro experiments treating EAC cell lines with 5-Aza-2'-Deoxycytidine (5-Aza-dC), short hairpin RNA knockdown and anticancer therapies. We identified and validated four methylation subtypes of EAC and BE. The high methylator subtype (HM) of EAC had the greatest number of activating events in We identified and characterised methylator subtypes in BE and EAC. We further demonstrated the biological and clinical relevance of EAC methylator subtypes, which may ultimately help guide clinical management of patients with EAC.
Identifiants
pubmed: 29884612
pii: gutjnl-2017-314544
doi: 10.1136/gutjnl-2017-314544
pmc: PMC6565505
mid: NIHMS990512
doi:
Substances chimiques
Antineoplastic Agents
0
DNA, Neoplasm
0
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
PTPN13 protein, human
EC 3.1.3.48
Protein Tyrosine Phosphatase, Non-Receptor Type 13
EC 3.1.3.48
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
389-399Subventions
Organisme : NIDDK NIH HHS
ID : T32 DK007742
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015704
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA150964
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA086402
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA182940
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK097948
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA152756
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA163060
Pays : United States
Informations de copyright
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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