Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis.
[erdheim-chester disease]
Langerhans
cell
histiocytosis
(
LCH
)
is
a
myeloproliferative
disorder
characterized
by
lesions
composed
of
pathological
CD
207
(
+
)
dendritic
cells
with
an
inflammatory
infiltrate
.
BRAFV
600
E
remains
the
only
recurrent
mutation
reported
in
LCH
.
In
order
to
evaluate
the
spectrum
of
somatic
mutations
in
LCH
,
whole
exome
sequencing
was
performed
on
matched
LCH
and
normal
tissue
samples
obtained
from
41
patients
.
Lesions
from
other
histiocytic
disorders
,
juvenile
xanthogranuloma
,
Erdheim-
Chester
disease
,
and
Rosai-
Dorfman
disease
were
also
evaluated
.
All
of
the
lesions
from
histiocytic
disorders
were
characterized
by
an
extremely
low
overall
rate
of
somatic
mutations
.
Notably
,
33
%
(
7
/
21
)
of
LCH
cases
with
wild-
type
BRAF
and
none
(
0
/
20
)
with
BRAFV
600
E
harbored
somatic
mutations
in
MAP
2
K
1
(
6
in
-frame
deletions
and
1
missense
mutation
)
that
induced
extracellular
signal-regulated
kinase
(
ERK
)
phosphorylation
in
vitro
.
Single
cases
of
somatic
mutations
of
the
mitogen-activated
protein
kinase
(
MAPK
)
pathway
genes
ARAF
and
ERBB
3
were
also
detected
.
The
ability
of
MAPK
pathway
inhibitors
to
suppress
MAPK
kinase
and
ERK
phosphorylation
in
cell
culture
and
primary
tumor
models
was
dependent
on
the
specific
LCH
mutation
.
The
findings
of
this
study
support
a
model
in
which
ERK
activation
is
a
universal
end
point
in
LCH
arising
from
pathological
activation
of
upstream
signaling
proteins
.
Diseases
Validation
Diseases presenting
"harbored somatic mutations"
symptom
erdheim-chester disease
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom