Cancer Discovery,
Год журнала:
2019,
Номер
9(11), С. 1493 - 1510
Опубликована: Окт. 14, 2019
Major
advances
in
our
understanding
of
cancer
pathogenesis
and
therapy
have
come
from
efforts
to
catalog
genomic
alterations
cancer.
A
growing
number
large-scale
studies
uncovered
mutations
that
drive
by
perturbing
cotranscriptional
post-transcriptional
regulation
gene
expression.
These
include
affect
each
phase
RNA
processing,
including
splicing,
transport,
editing,
decay
messenger
RNA.
The
discovery
these
events
illuminates
a
novel
therapeutic
vulnerabilities
generated
aberrant
processing
cancer,
several
which
progressed
clinical
development.
SIGNIFICANCE:
There
is
increased
recognition
genetic
affecting
splicing
polyadenylation
are
common
may
generate
opportunities.
Such
occur
within
an
individual
or
factors
themselves,
thereby
influencing
many
downstream
target
genes.
This
review
discusses
the
biological
impact
on
tumorigenesis
approaches
targeting
cells
bearing
mutations.
Nature Communications,
Год журнала:
2020,
Номер
11(1)
Опубликована: Апрель 20, 2020
Abstract
Metastatic
uveal
melanoma
is
less
well
understood
than
its
primary
counterpart,
has
a
distinct
biology
compared
to
skin
melanoma,
and
lacks
effective
treatments.
Here
we
genomically
profile
metastatic
tumors
infiltrating
lymphocytes.
BAP1
alterations
are
overrepresented
found
in
29/32
of
cases.
Reintroducing
functional
allele
into
deficient
patient-derived
cell
line,
reveals
broad
shift
towards
transcriptomic
subtype
previously
associated
with
better
prognosis
the
disease.
One
outlier
tumor
high
mutational
burden
UV-damage.
CDKN2A
deletions
also
occur,
which
rarely
present
primaries.
A
focused
knockdown
screen
used
investigate
overexpressed
genes
withcopy
number
gains.
Tumor-infiltrating
lymphocytes
several
cases
tumor-reactive,
but
expression
immune
checkpoint
receptors
TIM-3
,
TIGIT
LAG3
abundant.
This
study
represents
largest
whole-genome
analysis
date,
presents
an
updated
view
Cancer Discovery,
Год журнала:
2019,
Номер
9(11), С. 1493 - 1510
Опубликована: Окт. 14, 2019
Major
advances
in
our
understanding
of
cancer
pathogenesis
and
therapy
have
come
from
efforts
to
catalog
genomic
alterations
cancer.
A
growing
number
large-scale
studies
uncovered
mutations
that
drive
by
perturbing
cotranscriptional
post-transcriptional
regulation
gene
expression.
These
include
affect
each
phase
RNA
processing,
including
splicing,
transport,
editing,
decay
messenger
RNA.
The
discovery
these
events
illuminates
a
novel
therapeutic
vulnerabilities
generated
aberrant
processing
cancer,
several
which
progressed
clinical
development.
SIGNIFICANCE:
There
is
increased
recognition
genetic
affecting
splicing
polyadenylation
are
common
may
generate
opportunities.
Such
occur
within
an
individual
or
factors
themselves,
thereby
influencing
many
downstream
target
genes.
This
review
discusses
the
biological
impact
on
tumorigenesis
approaches
targeting
cells
bearing
mutations.
