International Journal of Cancer,
Journal Year:
2016,
Volume and Issue:
139(3), P. 647 - 656
Published: March 19, 2016
We
determined
prognostic
impact
of
KRAS,
BRAF,
PIK3CA
and
TP53
mutation
status
heterogeneity
among
164
colorectal
cancer
(CRC)
patients
undergoing
liver
resections
for
metastatic
disease.
Mutation
was
by
Sanger
sequencing
a
total
422
deposits.
In
univariate
analysis,
KRAS
(33.5%),
BRAF
(6.1%)
(13.4%)
mutations
each
predicted
reduced
median
time
to
relapse
(TTR)
(7
vs.
22,
3
16
4
17
months;
p
<
0.001,
0.002
0.023,
respectively).
also
disease-specific
survival
(DSS)
(29
51
49
<0.001
0.008,
No
effect
(60.4%)
observed.
Postoperative,
but
not
preoperative
chemotherapy
improved
both
TTR
DSS
(p
0.001
both)
with
no
interaction
gene
status.
Among
94
harboring
two
or
more
deposits,
13
revealed
across
deposits
at
least
one
gene.
compared
homogeneous
(18
37
=
0.011
all
genes;
26
analyzing
separately).
multivariate
analyses,
consistently
poor
TRR
DSS.
robustly
TTR,
while
postoperative
Our
findings
indicate
that
as
well
predict
outcome
in
CRC
subsequent
might
help
guide
treatment
decisions.
Cell,
Journal Year:
2021,
Volume and Issue:
184(8), P. 2239 - 2254.e39
Published: April 1, 2021
Intra-tumor
heterogeneity
(ITH)
is
a
mechanism
of
therapeutic
resistance
and
therefore
an
important
clinical
challenge.
However,
the
extent,
origin,
drivers
ITH
across
cancer
types
are
poorly
understood.
To
address
this,
we
extensively
characterize
whole-genome
sequences
2,658
samples
spanning
38
types.
Nearly
all
informative
(95.1%)
contain
evidence
distinct
subclonal
expansions
with
frequent
branching
relationships
between
subclones.
We
observe
positive
selection
driver
mutations
most
identify
type-specific
patterns
gene
mutations,
fusions,
structural
variants,
copy
number
alterations
as
well
dynamic
changes
in
mutational
processes
expansions.
Our
results
underline
importance
its
tumor
evolution
provide
pan-cancer
resource
comprehensively
annotated
events
from
sequencing
data.
Nature reviews. Cancer,
Journal Year:
2017,
Volume and Issue:
17(10), P. 605 - 619
Published: Sept. 15, 2017
Based
on
a
consensus
conference
of
experts
in
the
evolution
and
ecology
cancer,
this
article
proposes
framework
for
classifying
tumours
that
includes
four
evolutionary
ecological
processes:
neoplastic
cell
diversity
changes
over
time
diversity,
hazards
to
survival
available
resources.
Neoplasms
change
through
process
cell-level
evolution,
driven
by
genetic
epigenetic
alterations.
However,
microenvironment
determines
which
provide
adaptive
benefits.
There
is
widespread
recognition
importance
these
processes
but
date,
no
system
has
been
proposed
drawing
clinically
relevant
distinctions
between
how
different
are
evolving.
On
basis
fields
cancer
ecology,
we
propose
based
components.
These
cells
(intratumoural
heterogeneity)
make
up
an
index
(Evo-index),
as
well
resources
cells,
(Eco-index).
We
review
evidence
demonstrating
each
factors
describe
multiple
methods
can
be
used
measure
them.
Development
classification
holds
promise
enabling
clinicians
personalize
optimal
interventions
evolvability
patient's
tumour.
The
Evo-
Eco-indices
common
lexicon
communicating
about
neoplasms
response
interventions,
with
potential
implications
clinical
trials,
personalized
medicine
basic
research.
Cancer Discovery,
Journal Year:
2015,
Volume and Issue:
5(8), P. 806 - 820
Published: July 21, 2015
Our
understanding
of
cancer
is
being
transformed
by
exploring
clonal
diversity,
drug
resistance,
and
causation
within
an
evolutionary
framework.
The
therapeutic
resilience
advanced
a
consequence
its
character
as
complex,
dynamic,
adaptive
ecosystem
engendering
robustness,
underpinned
genetic
diversity
epigenetic
plasticity.
risk
mutation-driven
escape
self-renewing
cells
intrinsic
to
multicellularity
but
countered
multiple
restraints,
facilitating
increasing
complexity
longevity
species.
But
our
own
species
has
disrupted
this
historical
narrative
rapidly
escalating
risk.
Evolutionary
principles
illuminate
these
challenges
provide
new
avenues
explore
for
more
effective
control.
