Nature Biotechnology,
Journal Year:
2023,
Volume and Issue:
41(10), P. 1457 - 1464
Published: Feb. 6, 2023
DNA
comprises
molecular
information
stored
in
genetic
and
epigenetic
bases,
both
of
which
are
vital
to
our
understanding
biology.
Most
sequencing
approaches
address
either
genetics
or
epigenetics
thus
capture
incomplete
information.
Methods
widely
used
detect
bases
fail
common
C-to-T
mutations
distinguish
5-methylcytosine
from
5-hydroxymethylcytosine.
We
present
a
single
base-resolution
methodology
that
sequences
complete
the
two
most
cytosine
modifications
workflow.
is
copied
enzymatically
converted.
Coupled
decoding
across
original
copy
strand
provides
phased
digital
readout.
demonstrated
on
human
genomic
cell-free
blood
sample
patient
with
cancer.
The
approach
accurate,
requires
low
input
has
simple
workflow
analysis
pipeline.
Simultaneous,
reading
more
picture
genomes
applications
throughout
biomedicine.
Annals of Oncology,
Journal Year:
2022,
Volume and Issue:
33(8), P. 750 - 768
Published: July 6, 2022
•Validated
and
sensitive
ctDNA
assays
can
be
used
to
genotype
advanced
cancers
select
patients
for
targeted
therapies.•Initial
genotyping
with
should
considered
when
rapid
results
are
needed,
tissue
is
unavailable.•ctDNA
assay
limited
by
false-negative
results,
lower
sensitivity
fusion
events
copy
number
changes.•Use
of
detect
molecular
residual
disease
not
recommended,
due
lack
evidence
its
clinical
utility.
Circulating
tumour
DNA
(ctDNA)
conducted
on
plasma
rapidly
developing
a
strong
base
use
in
cancer.
The
European
Society
Medical
Oncology
convened
an
expert
working
group
review
the
analytical
validity
utility
assays.
For
cancer,
validated
adequately
have
identifying
actionable
mutations
direct
therapy,
may
routine
practice,
provided
limitations
taken
into
account.
Tissue-based
testing
remains
preferred
test
many
cancer
patients,
detecting
changes,
although
routinely
faster
will
clinically
important,
or
biopsies
possible
inappropriate.
Reflex
following
non-informative
result,
testing.
In
treated
early-stage
cancers,
detection
relapse,
has
high
anticipating
future
relapse
cancers.
Molecular
disease/molecular
cannot
recommended
as
currently
there
no
directing
treatment.
Additional
potential
applications
assays,
under
research
development
include
responding
therapy
early
dynamic
changes
levels,
monitoring
resistance
before
progression,
screening
asymptomatic
people
Recommendations
reporting
made.
Nature,
Journal Year:
2023,
Volume and Issue:
613(7943), P. 355 - 364
Published: Jan. 4, 2023
Abstract
DNA
methylation
is
a
fundamental
epigenetic
mark
that
governs
gene
expression
and
chromatin
organization,
thus
providing
window
into
cellular
identity
developmental
processes
1
.
Current
datasets
typically
include
only
fraction
of
sites
are
often
based
either
on
cell
lines
underwent
massive
changes
in
culture
or
tissues
containing
unspecified
mixtures
cells
2–5
Here
we
describe
human
methylome
atlas,
deep
whole-genome
bisulfite
sequencing,
allowing
fragment-level
analysis
across
thousands
unique
markers
for
39
types
sorted
from
205
healthy
tissue
samples.
Replicates
the
same
type
more
than
99.5%
identical,
demonstrating
robustness
programmes
to
environmental
perturbation.
Unsupervised
clustering
atlas
recapitulates
key
elements
ontogeny
identifies
patterns
retained
since
embryonic
development.
Loci
uniquely
unmethylated
an
individual
reside
transcriptional
enhancers
contain
binding
tissue-specific
regulators.
Uniquely
hypermethylated
loci
rare
enriched
CpG
islands,
Polycomb
targets
CTCF
sites,
suggesting
new
role
shaping
cell-type-specific
looping.
The
provides
essential
resource
study
regulation
disease-associated
genetic
variants,
wealth
potential
biomarkers
use
liquid
biopsies.
Cancer Cell,
Journal Year:
2022,
Volume and Issue:
40(12), P. 1537 - 1549.e12
Published: Nov. 17, 2022
In
the
Circulating
Cell-free
Genome
Atlas
(NCT02889978)
substudy
1,
we
evaluate
several
approaches
for
a
circulating
cell-free
DNA
(cfDNA)-based
multi-cancer
early
detection
(MCED)
test
by
defining
clinical
limit
of
(LOD)
based
on
tumor
allele
fraction
(cTAF),
enabling
performance
comparisons.
Among
10
machine-learning
classifiers
trained
same
samples
and
independently
validated,
when
evaluated
at
98%
specificity,
those
using
whole-genome
(WG)
methylation,
single
nucleotide
variants
with
paired
white
blood
cell
background
removal,
combined
scores
from
in
this
study
show
highest
cancer
signal
sensitivities.
Compared
stage
type,
cTAF
is
more
significant
predictor
classifier
may
closely
reflect
biology.
Clinical
LODs
mirror
relative
sensitivities
all
approaches.
The
WG
methylation
feature
best
predicts
origin.
most
promising
technology
MCED
informs
development
targeted
test.
Journal of Translational Medicine,
Journal Year:
2023,
Volume and Issue:
21(1)
Published: Feb. 11, 2023
Abstract
Cancer
is
a
worldwide
pandemic.
The
burden
it
imposes
grows
steadily
on
global
scale
causing
emotional,
physical,
and
financial
strains
individuals,
families,
health
care
systems.
Despite
being
the
second
leading
cause
of
death
worldwide,
many
cancers
do
not
have
screening
programs
people
with
high
risk
developing
cancer
fail
to
follow
advised
medical
regime
due
nature
available
tests
other
challenges
compliance.
Moreover,
liquid
biopsy
strategies
developed
for
early
detection
lack
sensitivity
required
detect
early-stage
cancers.
Early
key
improved
quality
life,
survival,
reduce
treatments
which
are
greater
at
later
stage
detection.
This
review
examines
current
market,
focusing
in
particular
strengths
drawbacks
techniques
achieving
We
explore
clinical
utility
technologies
earlier
solid
cancers,
focus
how
combination
various
spectroscopic
-omic
methodologies
may
pave
way
more
efficient
diagnostics.
CA A Cancer Journal for Clinicians,
Journal Year:
2022,
Volume and Issue:
73(4), P. 376 - 424
Published: Dec. 13, 2022
Abstract
Cancer
development
is
driven
by
the
accumulation
of
alterations
affecting
structure
and
function
genome.
Whereas
genetic
changes
disrupt
DNA
sequence,
epigenetic
contribute
to
acquisition
hallmark
tumor
capabilities
regulating
gene
expression
programs
that
promote
tumorigenesis.
Shifts
in
methylation
histone
mark
patterns,
two
main
modifications,
orchestrate
progression
metastasis.
These
cancer‐specific
events
have
been
exploited
as
useful
tools
for
diagnosis,
monitoring,
treatment
choice
aid
clinical
decision
making.
Moreover,
reversibility
contrast
irreversibility
changes,
has
made
machinery
an
attractive
target
drug
development.
This
review
summarizes
most
advanced
applications
biomarkers
drugs
setting,
highlighting
commercially
available
methylation‐based
assays
already
approved
US
Food
Drug
Administration.
