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
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