bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2021,
Volume and Issue:
unknown
Published: April 4, 2021
Abstract
Background
Transforming
patient-specific
molecular
data
into
clinical
decisions
is
fundamental
to
personalized
medicine.
Despite
massive
advancements
in
cancer
genomics,
date
driver
mutations
whose
frequencies
are
low,
and
their
observable
transformation
potential
minor
have
escaped
identification.
Yet,
when
paired
with
other
cis
,
such
‘latent
driver’
can
drive
cancer.
Here,
we
discover
double
mutations.
Method
We
applied
a
statistical
approach
identify
significantly
co-occurring
the
pan-cancer
of
mutation
profiles
∼80,000
tumor
sequences
from
TCGA
AACR
GENIE
databases.
The
components
same
gene
doublets
were
assessed
as
latent
drivers.
merged
analysis
significant
drug
response
cell
lines
patient
derived
xenografts
(PDXs).
This
allowed
us
link
impact
information
signatures
for
some
types.
Results
Our
comprehensive
identified
228
which
113
cataloged
Oncogenic
activation
protein
be
through
either
single
or
multiple
independent
mechanisms
action.
Combinations
driver,
weak
strong
leading
fully
activated
state
high
rate.
Tumor
suppressors
require
higher
mutational
load
coincide
compared
oncogenes
implies
relative
robustness
losing
functions.
Evaluation
patient-derived
xenograft
treatment
indicate
that
certain
genes
increase
oncogenic
activity,
hence
better
(e.g.
PIK3CA),
they
promote
resistance
drugs
EGFR).
Conclusion
allele
genome
landscapes
emphasizes
interrogation
big
genomic
integration
results
large-scale
small-molecule
sensitivity
provide
deep
patterns
rare;
but
still
result
dramatic
phenotypic
alterations,
Research Square (Research Square),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Dec. 1, 2023
Abstract
Inactivating
mutations
of
genes
encoding
the
cohesin
complex
are
common
in
a
wide
range
human
cancers.
STAG2
is
most
commonly
mutated
subunit.
Here
we
report
impact
stable
correction
endogenous,
naturally
occurring
on
gene
expression,
3D
genome
organization,
chromatin
loops,
and
Polycomb
signaling
glioblastoma
multiforme
(GBM).
In
two
GBM
cell
lines,
their
significantly
altered
expression
~10%
all
expressed
genes.
Virtually
highly
regulated
were
negatively
by
(i.e.,
higher
STAG2-mutant
cells
than
STAG2-corrected
cells),
one
them
–
HEPH
was
uncultured
tumors
as
well.
While
had
little
effect
large
scale
features
organization
(A/B
compartments,
TADs),
did
alter
thousands
individual
some
which
controlled
adjacent
Loops
specific
to
cells,
STAG1-containing
complexes,
very
large,
supporting
prior
findings
that
complexes
have
greater
loop
extrusion
processivity
STAG2-containing
suggesting
long
loops
may
be
general
feature
Finally,
STAG2-regulated
enriched
for
H3K27me3
epigenetic
mark,
revealing
inactivation
can
activate
GBM,
identifying
potential
target
therapeutic
intervention
tumors.
Together,
these
illuminate
landscape
genes,
A/B
pathways
providing
important
clues
into
largely
still
unknown
mechanism
tumor
suppression.
Clinical and Experimental Health Sciences,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 7, 2024
Objective:
Anomalies
in
the
cohesion
complex
contribute
to
pathogenesis
of
myeloid
malignancies
by
affecting
self-renewal
capacity
hematopoietic
and
progenitor
stem
cells,
but
underlying
mechanisms
this
phenotype
are
not
fully
understood.
Therefore,
study
aims
shed
light
on
relationship
between
AML
comprehensively
determining
mutations
expression
profiles
genes
constituting
investigating
effect
survival
using
bioinformatics
databases
tools.
Methods:
A
total
96
different
were
identified
13
genes.
Out
these
mutations,
26
classified
as
pathogenic/oncogenic.
The
levels
STAG1,
REC8,
MAU2,
CDCA5,
PDS5B
significantly
higher
patient
group
compared
healthy
(p<
.01).
Survival
analysis
based
low
high
gene
revealed
that
increased
REC8
was
associated
with
(p=
.024),
which
is
considered
a
prognostic
marker.
In
STRING
analysis,
it
determined
hub
proteins
interact
acetyltransferases
ESCO1
ESCO2
involved
sister
chromatid
cohesion,
TERF1,
component
telomere
nucleoprotein
complex,
PDS5A
BRCA2,
functionally
related
genetic
stability
recombination,
respectively.
Results:
An
increase
language
outcomes,
particularly
repetition,
observed
following
treatments.
It
also
found
therapy
gains
more
robust
bihemispheric
stimulation
posterior
temporal
sites
inferior
frontal
targets.
Conclusion:
Overall,
none
target
except
mutated
showed
significant
independent
clinical
outcome
defined
overall
survival.
However,
we
have
diversity
alterations
individual
cohesin
subunits
through
comprehensive
molecular
analysis.
results
may
be
beneficial
development
targeted
drug
therapies
personalized
medicine
approaches.
Scientific Reports,
Journal Year:
2022,
Volume and Issue:
12(1)
Published: July 29, 2022
Abstract
Somatic
mutations
and
changes
in
expression
of
RAD21
are
common
many
types
cancer.
Moreover,
sub-optimal
levels
early
development
can
result
cohesinopathies.
Altered
directly
from
the
gene.
However,
whether
DNA
variants
outside
gene
could
control
its
thereby
contribute
to
cancer
developmental
disease
is
unknown.
In
this
study,
we
searched
for
genomic
that
modify
determine
their
potential
or
by
dysregulation.
We
42,953,834
a
spatial-eQTL
association
with
transcription
RAD21.
identified
123
significant
associations
(FDR
<
0.05),
which
local
(
cis
)
long-distance
trans
regulators
expression.
The
co-regulate
further
seven
genes
AARD
,
AKAP11
GRID1
KCNIP4
RCN1
TRIOBP
USP32
),
enriched
having
Sp2
factor
binding
sites
promoter
regions.
six
had
previously
been
associated
onset,
progression,
metastasis.
Our
results
suggest
genome-wide
variation
non-coding
regions
impacts
on
transcript
addition
other
genes,
then
impact
oncogenesis
process
ubiquitination.
This
identification
distant
co-regulation
oncogenes
represents
strategy
discovery
novel
genetic
influencing
onset
diagnostics.
Briefings in Functional Genomics,
Journal Year:
2021,
Volume and Issue:
unknown
Published: Feb. 3, 2021
In
recent
years,
remarkable
progress
has
been
made
toward
understanding
the
three-dimensional
(3D)
organisation
of
genomes
and
influence
genome
on
gene
regulation.
Although
3D
probably
plays
a
crucial
role
in
embryo
development,
animal
studies
addressing
developmental
roles
chromosome
topology
are
only
just
starting
to
emerge.
Zebrafish,
an
important
model
system
for
early
have
already
contributed
advances
consequences
perturbation
organisation.
Zebrafish
used
determine
effects
mutations
proteins
responsible
organisation:
cohesin
CTCF.
this
review,
we
highlight
research
date
from
zebrafish
that
provided
insight
into
how
contributes
tissue-specific
regulation
development.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2021,
Volume and Issue:
unknown
Published: April 4, 2021
Abstract
Background
Transforming
patient-specific
molecular
data
into
clinical
decisions
is
fundamental
to
personalized
medicine.
Despite
massive
advancements
in
cancer
genomics,
date
driver
mutations
whose
frequencies
are
low,
and
their
observable
transformation
potential
minor
have
escaped
identification.
Yet,
when
paired
with
other
cis
,
such
‘latent
driver’
can
drive
cancer.
Here,
we
discover
double
mutations.
Method
We
applied
a
statistical
approach
identify
significantly
co-occurring
the
pan-cancer
of
mutation
profiles
∼80,000
tumor
sequences
from
TCGA
AACR
GENIE
databases.
The
components
same
gene
doublets
were
assessed
as
latent
drivers.
merged
analysis
significant
drug
response
cell
lines
patient
derived
xenografts
(PDXs).
This
allowed
us
link
impact
information
signatures
for
some
types.
Results
Our
comprehensive
identified
228
which
113
cataloged
Oncogenic
activation
protein
be
through
either
single
or
multiple
independent
mechanisms
action.
Combinations
driver,
weak
strong
leading
fully
activated
state
high
rate.
Tumor
suppressors
require
higher
mutational
load
coincide
compared
oncogenes
implies
relative
robustness
losing
functions.
Evaluation
patient-derived
xenograft
treatment
indicate
that
certain
genes
increase
oncogenic
activity,
hence
better
(e.g.
PIK3CA),
they
promote
resistance
drugs
EGFR).
Conclusion
allele
genome
landscapes
emphasizes
interrogation
big
genomic
integration
results
large-scale
small-molecule
sensitivity
provide
deep
patterns
rare;
but
still
result
dramatic
phenotypic
alterations,