bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2017,
Volume and Issue:
unknown
Published: Sept. 20, 2017
SUMMARY
The
advance
of
personalized
cancer
medicine
requires
the
accurate
identification
mutations
driving
each
patient’s
tumor.
However,
to
date,
we
have
only
been
able
obtain
partial
insights
into
contribution
genomic
events
tumor
development.
Here,
design
a
comprehensive
approach
identify
driver
in
and
whole-genome
panorama
across
more
than
2,500
tumors
from
37
types
cancer.
This
includes
coding
non-coding
point
mutations,
copy
number
alterations
other
rearrangements
somatic
origin,
potentially
predisposing
germline
variants.
We
demonstrate
that
are
at
root
virtually
all
tumors,
with
carrying
on
average
4.6
events.
Most
individual
harbor
unique
combination
drivers,
uncover
most
frequent
co-occurring
Half
genes
affected
by
several
mutations.
In
summary,
described
here
provides
answers
fundamental
questions
genomics
bridges
gap
between
medicine.
Cell,
Journal Year:
2017,
Volume and Issue:
171(5), P. 1029 - 1041.e21
Published: Oct. 19, 2017
Cancer
develops
as
a
result
of
somatic
mutation
and
clonal
selection,
but
quantitative
measures
selection
in
cancer
evolution
are
lacking.
We
adapted
methods
from
molecular
applied
them
to
7,664
tumors
across
29
types.
Unlike
species
evolution,
positive
outweighs
negative
during
development.
On
average,
<1
coding
base
substitution/tumor
is
lost
through
with
purifying
almost
absent
outside
homozygous
loss
essential
genes.
This
allows
exome-wide
enumeration
all
driver
mutations,
including
known
carry
∼4
substitutions
under
ranging
<1/tumor
thyroid
testicular
cancers
>10/tumor
endometrial
colorectal
cancers.
Half
occur
yet-to-be-discovered
With
increasing
burden,
numbers
mutations
increase,
not
linearly.
systematically
catalog
genes
show
that
vary
extensively
what
proportion
drivers
versus
passengers.
Science,
Journal Year:
2020,
Volume and Issue:
367(6483), P. 1264 - 1269
Published: March 12, 2020
In
most
human
cancers,
only
a
few
genes
are
mutated
at
high
frequencies;
low
frequencies.
The
functional
consequences
of
these
recurrent
but
infrequent
"long
tail"
mutations
often
unknown.
We
focused
on
484
long
tail
in
head
and
neck
squamous
cell
carcinoma
(HNSCC)
used
vivo
CRISPR
to
screen
for
that,
upon
mutation,
trigger
tumor
development
mice.
Of
the
15
tumor-suppressor
identified,
ADAM10
AJUBA
suppressed
HNSCC
haploinsufficient
manner
by
promoting
NOTCH
receptor
signaling.
or
monoallelic
loss
occur
28%
cases
mutually
exclusive
with
mutations.
Our
results
show
that
oncogenic
67%
converge
onto
signaling
pathway,
making
inactivation
hallmark
HNSCC.
ESMO Open,
Journal Year:
2016,
Volume and Issue:
1(5), P. e000094 - e000094
Published: Jan. 1, 2016
We
live
in
an
era
of
genomic
medicine.
The
past
five
years
brought
about
many
significant
achievements
the
field
cancer
genetics,
driven
by
rapidly
evolving
technologies
and
plummeting
costs
next-generation
sequencing
(NGS).
official
completion
Cancer
Genome
Project
2014
led
to
envision
clinical
implementation
data
as
next
logical
step
therapy.
Stemming
from
this
vision,
term
'precision
oncology'
was
coined
illustrate
novelty
individualised
approach.
basic
assumption
precision
oncology
is
that
molecular
markers
detected
NGS
will
predict
response
targeted
therapies
independently
tumour
histology.
However,
along
with
a
ubiquitous
availability
NGS,
complexity
heterogeneity
at
individual
patient
level
had
be
acknowledged.
Not
only
does
latter
present
challenges
decision-making
based
on
data,
it
also
obstacle
rational
design
trials.
Novel
tissue-agnostic
trial
designs
were
quickly
developed
overcome
these
challenges.
Results
some
trials
have
recently
demonstrated
feasibility
efficacy
On
other
hand,
there
increasing
amount
whole-exome
whole-genome
which
allows
us
assess
ever
smaller
differences
between
patients
cancer.
In
review,
we
highlight
different
strategies
currently
used
for
oncology,
describe
their
strengths
weaknesses,
emphasise
settings.
Further,
evaluate
possibility
current
future
trials,
point
significance
translational
research.
Nature Communications,
Journal Year:
2017,
Volume and Issue:
8(1)
Published: Sept. 6, 2017
Esophageal
squamous
dysplasia
is
believed
to
be
the
precursor
lesion
of
esophageal
cell
carcinoma
(ESCC);
however,
genetic
evolution
from
ESCC
remains
poorly
understood.
Here,
we
applied
multi-region
whole-exome
sequencing
samples
two
cohorts,
45
patients
with
matched
and
samples,
13
tumor-free
only
samples.
Our
analysis
reveals
that
heavily
mutated
harbors
most
driver
events
reported
in
ESCC.
Moreover,
polyclonal,
remarkable
heterogeneity
often
observed
between
tumors
their
neighboring
Notably,
copy
number
alterations
are
prevalent
persist
during
progression,
which
distinct
development
adenocarcinoma.
The
sharp
contrast
prevalence
'two-hit'
event
on
TP53
cohorts
suggests
complete
inactivation
essential
promoting
ESCC.The
pathogenesis
oesophageal
a
multi-step
process
but
determinants
behind
this
progression
unknown.
Here
authors
use
exome
comprehensively
investigate
dysplastic
lesions
untransformed
oesophagus.
