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Epigenetics in the Pathogenesis of Esophageal Adenocarcinoma.
[esophageal adenocarcinoma]
Epigenetic
influences
,
such
as
DNA
methylation
,
histone
acetylation
,
and
up-regulation
/
down-regulation
of
genes
by
microRNAs
,
change
the
genetic
makeup
of
an
individual
without
affecting
DNA
base-pair
sequences
.
Indeed
,
epigenetic
changes
play
an
integral
role
in
the
progression
from
normal
esophageal
mucosa
to
Barrett
's
esophagus
to
esophageal
adenocarcinoma
via
dysplasia-metaplasia-
neoplasia
sequence
.
Many
genes
involved
in
esophageal
adenocarcinoma
display
hypermethylation
,
leading
to
their
down-regulation
.
The
classes
of
these
genes
include
cell
cycle
control
,
DNA
and
growth
factor
repair
,
tumor
suppressors
,
antimetastasis
,
Wnt-related
genes
,
and
proapoptotic
genes
.
Histone
acetylation
in
the
pathophysiology
of
esophageal
diseases
has
not
been
thoroughly
investigated
,
and
its
critical
role
in
the
development
of
esophageal
adenocarcinoma
is
less
defined
.
Many
microRNAs
have
been
associated
with
the
development
of
Barrett
's
esophagus
and
esophageal
adenocarcinoma
.
Here
,
we
critically
addressed
the
specific
steps
most
closely
influenced
by
microRNAs
in
the
progression
from
Barrett
's
esophagus
to
esophageal
adenocarcinoma
.
However
,
microRNAs
can
target
up
to
hundreds
of
genes
,
making
it
difficult
to
correlate
directly
with
a
given
phenotype
of
the
disease
.
Esophageal
adenocarcinoma
progressing
from
premalignant
condition
of
Barrett
's
esophagus
carries
an
extremely
poor
prognosis
.
Risk
stratification
for
patients
based
on
their
epigenetic
profiles
may
be
useful
in
providing
more
targeted
and
directed
treatment
to
patients
.
Diseases
Validation
Diseases presenting
"extremely poor prognosis"
symptom
esophageal adenocarcinoma
esophageal squamous cell carcinoma
junctional epidermolysis bullosa
primary effusion lymphoma
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