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Copy number losses define subgroups of dedifferentiated liposarcoma with poor prognosis and genomic instability.
[dedifferentiated liposarcoma]
Molecular
events
underlying
progression
of
well-differentiated
liposarcoma
(
WDLS
)
to
dedifferentiated
liposarcoma
(
DDLS
)
are
poorly
defined
.
This
study
sought
to
identify
copy
number
alterations
(
CNA
)
associated
with
dedifferentiation
of
WDLS
,
with
DDLS
morphology
,
and
with
patient
outcomes
.
Fifty
-
five
WDLS
and
52
DDLS
were
analyzed
using
Agilent
244
K
comparative
genomic
hybridization
and
Affymetrix
U
133
A
expression
arrays
.
CNAs
were
identified
by
RAE
analysis
.
Thirty
-
nine
of
the
DDLS
specimens
were
categorized
morphologically
by
a
single
pathologist
.
Nine
regions
of
CNA
were
identified
as
recurrent
in
DDLS
but
not
WDLS
;
79
%
of
DDLS
had
at
least
one
of
these
CNAs
.
Loss
of
the
chromosome
segment
11
q
23
-
24
,
the
most
common
event
,
was
observed
only
in
DDLS
that
morphologically
resembled
the
genomically
complex
sarcomas
,
undifferentiated
pleomorphic
sarcoma
and
myxofibrosarcoma
.
11
q
23
-
24
loss
was
itself
associated
with
increased
genomic
complexity
in
DDLS
.
Loss
of
19
q
13
,
but
not
11
q
23
-
24
,
was
associated
with
poor
prognosis
.
Median
disease-
specific
survival
was
shorter
for
patients
with
19
q
13
loss
(
27
months
)
than
for
patients
with
diploid
19
q
13
(
>
90
months
;
P
<
0
.
0025
)
,
and
19
q
13
loss
was
associated
with
local
recurrence
(
HR
,
2
.
86
;
P
=
0
.
013
)
.
Common
copy
number
losses
were
associated
with
transcriptional
downregulation
of
potential
tumor
suppressors
and
adipogenesis-related
genes
(
e
.
g
.
,
EI
24
and
CEBPA
)
.
Dedifferentiation
of
WDLS
is
associated
with
recurrent
CNAs
in
79
%
of
tumors
.
In
DDLS
,
loss
of
11
q
23
-
24
is
associated
with
genomic
complexity
and
distinct
morphology
whereas
loss
of
19
q
13
predicts
poor
prognosis
.
CNAs
in
liposarcoma
improve
risk
stratification
for
patients
and
will
help
identify
potential
tumor
suppressors
driving
liposarcoma
progression
.
Diseases
Validation
Diseases presenting
"tumor suppressors"
symptom
cholangiocarcinoma
dedifferentiated liposarcoma
esophageal adenocarcinoma
esophageal squamous cell carcinoma
lymphangioleiomyomatosis
werner syndrome
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