Esophageal Adenocarcinoma Methods and Protocols

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for DNA methylation is 5′-CpG-3′ dinucleotides (CpG islands).

CpG islands are small stretches of DNA about 300–3000 bp, which

usually have >50% GC content and they are located at the 5′ regula-

tory regions. About 70% of promoter regions contain CpG islands

and only 1% of remaining genome contains CpG islands. Methyl

group is covalently added at the 5′ side of the cytosine ring by CpG

methyltransferases and demethylation may involve TET proteins or

oxidative pathways leading to intermediates.

Table 1
Methylation of genes involved in the pathogenesis of esophageal adenocarcinomas

Gene Function in cells Significance in esophageal adenocarcinoma Reference

CDKN2AControl cell cycle Promoter methylation inactivated its expression and

associated with premalignant lesion and

adenocarcinoma

[ 5 , 8 ]

MGMT Regulate DNA repair Methylation mediated inactivation associated with

the progression of the disease stages

[ 14 ]

IGFBP7 Modulate binding of

IGF factors to its

receptors

Promoter methylation correlated with poor

prognosis in patients with esophageal

adenocarcinoma

[ 15 ]

APC Involve is cell adhesion Promoter methylation associated with poor

prognosis and recurrence of cancer

[ 16 , 17 ]

DAMK1 Regulate apoptosis Hypermethylation mediated loss or silencing of

DAMK1 protein associated with depth of tumour

invasion and advanced tumour stages

[ 18 ]

CDH13 Modulate cell adhesion,

proliferation,

metastasis

Methylation associated with the segment length of

Barrett esophagus

[ 19 ]

NELL1 Regulate cell growth

and differentiation

Hypermethylation significantly associated with

shorter survival time of patients with esophageal

adenocarcinoma

[ 20 ]

SOCS Suppressor of JAK/

STAT pathway

Promoter hypermethylation and subsequent

silencing of SOCS family proteins involved in the

multi-steps pathogenesis of esophageal

adenocarcinoma

[ 21 ]

TAC1 Involve in cell

proliferation and

apoptosis

Promoter hypermethylation correlated with the

progression of esophageal adenocarcinoma

[ 22 ]

WIF1 Wnt-signalling pathway

inhibitor

Silencing of WIF1 through promotor methylation is

an early event of Barrett esophagus and

esophageal adenocarcinoma

[ 23 ]

CDKN2A cyclin-dependent kinase Inhibitor 2A, MGMT O-Methylguanine-DNA Methyltransferase, IGFBP7 Insulin-
like growth factor-binding protein 7, APC adenomatous polyposis coli, DAMK1 Death-associated protein kinase1,
CDH13 Cadherin 13, NELL1 The nel-like1, SOCS Suppressor of Cytokine signaling, TAC1 The tachykinin-1, WIF1
WNT Inhibitory Factor 1

DNA Methylation in Esophageal Adenocarcinoma