Rare Diseases Symptoms Automatic Extraction
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A random Abstract
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Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis.
[esophageal adenocarcinoma]
Oesophageal
adenocarcinoma
(
EAC
)
incidence
is
rapidly
increasing
in
Western
countries
.
A
better
understanding
of
EAC
underpins
efforts
to
improve
early
detection
and
treatment
outcomes
.
While
large
EAC
exome
sequencing
efforts
to
date
have
found
recurrent
loss
-of-function
mutations
,
oncogenic
driving
events
have
been
underrepresented
.
Here
we
use
a
combination
of
whole-genome
sequencing
(
WGS
)
and
single
-nucleotide
polymorphism-array
profiling
to
show
that
genomic
catastrophes
are
frequent
in
EAC
,
with
almost
a
third
(
32
%
,
n
=
40
/
123
)
undergoing
chromothriptic
events
.
WGS
of
22
EAC
cases
show
that
catastrophes
may
lead
to
oncogene
amplification
through
chromothripsis-derived
double
-
minute
chromosome
formation
(
MYC
and
MDM
2
)
or
breakage-
fusion
-bridge
(
KRAS
,
MDM
2
and
RFC
3
)
.
Telomere
shortening
is
more
prominent
in
EACs
bearing
localized
complex
rearrangements
.
Mutational
signature
analysis
also
confirms
that
extreme
genomic
instability
in
EAC
can
be
driven
by
somatic
BRCA
2
mutations
.
These
findings
suggest
that
genomic
catastrophes
have
a
significant
role
in
the
malignant
transformation
of
EAC
.
Diseases
Validation
Diseases presenting
"loss-of-function mutations"
symptom
achondroplasia
alpha-thalassemia
aromatase deficiency
child syndrome
cowden syndrome
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erythropoietic protoporphyria
esophageal adenocarcinoma
familial hypocalciuric hypercalcemia
harlequin ichthyosis
hirschsprung disease
kallmann syndrome
kindler syndrome
lamellar ichthyosis
neonatal adrenoleukodystrophy
pendred syndrome
werner syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated