Genome Research,
Год журнала:
2019,
Номер
29(3), С. 418 - 427
Опубликована: Фев. 26, 2019
Cell-free
DNA
(cfDNA)
in
human
plasma
is
a
class
of
biomarkers
with
many
current
and
potential
future
diagnostic
applications.
Recent
studies
have
shown
that
cfDNA
molecules
are
not
randomly
fragmented
possess
information
related
to
their
tissues
origin.
Pathologies
causing
death
cells
from
particular
result
perturbations
the
relative
distribution
affected
tissues.
Such
tissue-of-origin
analysis
particularly
useful
development
liquid
biopsies
for
cancer.
It
therefore
value
accurately
determine
contributions
pool
simultaneous
manner.
In
this
work,
we
report
open
chromatin
regions,
show
characteristic
fragmentation
patterns
reflected
by
sequencing
coverage
imbalance
differentially
phased
fragment
end
signals.
The
latter
refers
differences
read
densities
sequences
corresponding
orientation
upstream
downstream
ends
relation
reference
genome.
preferentially
occur
tissue-specific
regions
where
contributed
into
plasma.
Quantitative
analyses
such
signals
allow
measurement
various
toward
pool.
These
findings
were
validated
data
obtained
pregnant
women,
organ
transplantation
recipients,
cancer
patients.
Orientation-aware
has
applications
noninvasive
prenatal
testing,
monitoring,
biopsy.
Liquid
biopsies
that
analyze
cell-free
DNA
in
blood
plasma
are
used
for
noninvasive
prenatal
testing,
oncology,
and
monitoring
of
organ
transplant
recipients.
molecules
released
into
the
from
various
bodily
tissues.
Physical
molecular
features
fragments
their
distribution
over
genome
bear
information
about
tissues
origin.
Moreover,
patterns
methylation
these
reflect
those
tissue
sources.
The
nucleosomal
organization
nuclease
content
origin
affect
fragmentation
profile
molecules,
such
as
fragment
size
end
motifs.
Besides
double-stranded
linear
fragments,
other
topological
forms
also
exist-namely
circular
single-stranded
molecules.
Enhanced
by
features,
liquid
hold
promise
detection
tissue-specific
pathologies
with
a
range
clinical
applications.
Cancer Biology & Therapy,
Год журнала:
2019,
Номер
20(8), С. 1057 - 1067
Опубликована: Апрель 16, 2019
Tumor-specific,
circulating
cell-free
DNA
in
liquid
biopsies
is
a
promising
source
of
biomarkers
for
minimally
invasive
serial
monitoring
treatment
responses
cancer
management.
We
will
review
the
current
understanding
origin
and
different
forms
release
(including
various
types
cell
death
active
secretion
processes)
clearance
routes.
The
dynamics
extracellular
blood
during
therapy
role
pathophysiological
processes
(tumor-associated
inflammation,
NETosis,
pre-metastatic
niche
development)
provide
insights
into
mechanisms
that
contribute
to
tumor
development
metastases
formation.
Better
knowledge
tumor-specific
could
facilitate
new
therapeutic
diagnostic
options
Frontiers in Genetics,
Год журнала:
2019,
Номер
10
Опубликована: Ноя. 14, 2019
Carcinogenesis
is
accompanied
by
widespread
DNA
methylation
changes
within
the
cell.
These
are
characterised
a
globally
hypomethylated
genome
with
focal
hypermethylation
of
numerous
5'-cytosine-phosphate-guanine-3'
(CpG)
islands,
often
spanning
gene
promoters
and
first
exons.
Many
these
epigenetic
occur
early
in
tumorigenesis
highly
pervasive
across
tumour
type.
This
allows
cancer
biomarkers
to
be
suitable
for
detection
also
have
utility
range
areas
relevant
treatment.
Such
tests
simple
construction,
as
only
one
or
few
loci
need
targeted
good
test
coverage.
properties
make
cancer-associated
very
attractive
development
biomarker
substantive
clinical
utility.
Across
patient
journey
from
initial
detection,
treatment
then
monitoring,
there
several
points
where
assays
can
inform
practice.
Assays
on
surgically
removed
tissue
useful
determine
indicators
resistance,
prognostication
outcome
molecularly
characterise,
classify
origin
tumour.
Cancer-associated
detected
accuracy
cell-free
present
blood,
stool,
urine
other
biosamples.
hold
great
promise
simple,
economical
specific
population-wide
screening,
successfully
translated
examples
already.
The
ability
circulating
liquid
biopsy
monitor
situ
response
therapy,
detect
minimal
residual
disease
an
recurrence.
review
will
summarise
existing
used
practice
application
domains
above,
discuss
what
makes
identify
barriers
translation.
We
technical
factors
such
analytical
performance
product-market
fit,
that
contribute
successful
downstream
investment,
including
geography,
how
this
impacts
intellectual
property
(IP),
regulatory
hurdles
future
marketplace
healthcare
system.
British Journal of Cancer,
Год журнала:
2020,
Номер
124(2), С. 345 - 358
Опубликована: Сен. 24, 2020
Abstract
Cell-free
DNA
(cfDNA)
derived
from
tumours
is
present
in
the
plasma
of
cancer
patients.
The
majority
currently
available
studies
on
use
this
circulating
tumour
(ctDNA)
deal
with
detection
mutations.
analysis
cfDNA
often
discussed
context
noninvasive
mutations
that
lead
to
resistance
mechanisms
and
therapeutic
disease
monitoring
Indeed,
substantial
advances
have
been
made
area,
development
methods
reach
high
sensitivity
can
interrogate
a
large
number
genes.
Interestingly,
however,
also
be
used
analyse
different
features
DNA,
such
as
methylation
status,
size
fragment
patterns,
transcriptomics
viral
load,
which
open
new
avenues
for
liquid
biopsy
samples
This
review
will
focus
perspectives
challenges
mutation
patients
solid
malignancies.
There
is
a
growing
trend
towards
exploring
the
use
of
minimally
invasive
"liquid
biopsy"
to
identify
biomarkers
in
number
cancers,
including
urologic
malignancies.
Multiple
aspects
can
be
assessed
circulating
cell-free
DNA,
DNA
levels,
integrity,
methylation
and
mutations.
Other
prospective
liquid
biopsy
markers
include
tumor
cells,
RNAs
(miRNA,
lncRNAs
mRNAs),
proteins,
peptides
exosomes
have
also
emerged
as
non-invasive
cancer
biomarkers.
These
molecules
detected
various
biological
fluids,
blood,
urine,
saliva
seminal
plasma.
Liquid
biopsies
hold
great
promise
for
personalized
medicine
due
their
ability
provide
multiple
global
snapshots
primary
metastatic
tumors.
Molecular
profiling
has
been
stepping-stone
successful
introduction
several
multi-marker
tests
into
clinic.
In
this
review,
we
an
overview
current
state
DNA-based
kidney,
prostate
bladder
biomarker
research
discuss
potential
utility
other
molecules.
We
will
challenges
limitations
facing
discovery
benefits
area
translational
research.
Clinical Genetics,
Год журнала:
2019,
Номер
95(6), С. 643 - 660
Опубликована: Янв. 24, 2019
Breast
cancer
is
the
most
common
among
women
worldwide.
Due
to
its
complexity
in
nature,
effective
breast
treatment
can
encounter
many
challenges.
Traditional
methods
of
detection
such
as
tissue
biopsy
are
not
comprehensive
enough
capture
entire
genomic
landscape
tumors.
However,
with
introduction
novel
techniques,
application
liquid
has
been
enhanced,
enabling
improvement
various
aspects
management
including
early
diagnosis
and
screening,
prediction
prognosis,
relapse,
serial
sampling
efficient
longitudinal
monitoring
disease
progress
response
treatment.
Various
components
tumor
cells
released
into
blood
circulation
be
analyzed
sampling,
some
which
include
circulating
(CTCs),
DNA
(ctDNA),
cell‐free
RNA,
tumor‐educated
platelets
exosomes.
These
utilized
for
different
purposes.
As
an
example,
ctDNA
sequenced
genetic
profiling
tumors
enhance
individualized
screening.
CTC
plasma
count
analysis
or
after
curative
resection
surgery
could
facilitate
minimal
residual
disease,
aiding
initiation
adjuvant
therapy
prevent
recurrence.
Furthermore,
assessed
determine
stage
prognosis
cancer.
In
this
review,
we
discuss
advantages
limitations
used
will
expand
on
that
require
further
focus
future
research.
Biological reviews/Biological reviews of the Cambridge Philosophical Society,
Год журнала:
2018,
Номер
93(3), С. 1649 - 1683
Опубликована: Апрель 14, 2018
ABSTRACT
Since
the
detection
of
cell‐free
DNA
(cfDNA)
in
human
plasma
1948,
it
has
been
investigated
as
a
non‐invasive
screening
tool
for
many
diseases,
especially
solid
tumours
and
foetal
genetic
abnormalities.
However,
to
date
our
lack
knowledge
regarding
origin
purpose
cfDNA
physiological
environment
limited
its
use
more
obvious
diagnostics,
neglecting,
example,
potential
utility
identification
predisposition
disease,
earlier
cancers,
lifestyle‐induced
epigenetic
changes.
Moreover,
concept
or
mechanism
could
also
have
therapeutic
uses
such
immuno‐
gene
therapy.
This
review
presents
an
extensive
compilation
putative
origins
then
contrasts
contributions
cellular
breakdown
processes
with
active
mechanisms
release
into
extracellular
environment.
The
involvement
derived
from
both
lateral
information
transfer
is
discussed.
We
hope
encourage
researchers
adopt
holistic
view
research,
taking
account
all
biological
pathways
which
involved,
give
serious
consideration
integration
vitro
vivo
research.
wish
not
limit
their
focus
apoptotic
necrotic
fraction
cfDNA,
but
investigate
intercellular
messaging
capabilities
actively
released
study
role
pathogenesis.
Characterizing
and
monitoring
tumor
genomes
with
blood
samples
could
achieve
significant
improvements
in
precision
medicine.
As
tumors
shed
parts
of
themselves
into
the
circulation,
analyses
circulating
cells,
DNA,
tumor-derived
exosomes,
often
referred
to
as
“liquid
biopsies”,
may
enable
genome
characterization
by
minimally
invasive
means.
Indeed,
multiple
studies
have
described
how
molecular
information
about
parent
can
be
extracted
from
these
components.
Here,
we
briefly
summarize
current
technologies
then
elaborate
on
emerging
novel
concepts
that
further
propel
field.
We
address
normal
detectable
mutation
levels
context
our
knowledge
regarding
gradual
accumulation
mutations
during
aging
light
technological
limitations.
Finally,
discuss
whether
liquid
biopsies
are
ready
used
routine
clinical
practice.
