0:00
Hello.
I am Roderick Beijersbergen
from the Netherlands
Cancer Institute in Amsterdam.
And I will be talking
to you today
about functional
cancer genomics.
0:10
In the past decade,
rapid progress in the ability
to analyze
full genomes of cancers
has pointed out
that individual tumors
may contain hundreds
and thousand of mutations
across the entire genome.
Some tumors, such as
colorectal cancer, lung cancer
and melanoma, have frequently
even up to a 100,000 mutations.
Although the majority
of these mutations
will not directly affect
the coding region of genes,
and thus, not lead
to abnormal proteins,
estimates are that
10 to 100 mutations expressed
in coding regions will
result in the expression
of mutant proteins
with aberrant functions.
These abnormal proteins
and the biological pathways
and mechanisms they control
play important roles
in the development of cancer
and response
to cancer therapies.
It's an enormous challenge
for oncology research to map
and understand the role of each
of these genetic alterations
for the diagnosis, prognosis
and treatment of cancer.
In addition to the large
numbers of mutations
found in different tumor types,
it has also become clear
that within one tumor type,
for example lung cancer,
different mutational spectra
can be found
in individual patients.
1:19
This slide shows significantly
mutated genes
in 178 tumors of one type,
in this example,
squamous cell lung cancer.
Although the frequency
of the mutations
of the tumor suppressor
gene TP53 is high,
with more than
80 percent mutation frequency,
for other genes, even though
they are significantly mutated,
this mutation rate
is much lower.
This indicates that among
different tumors,
different mutations exist,
even within one tumor type.
This heterogeneity
among different tumors,
even from the same tumor type,
complicates the interpretation
and use of
this genetic information
for the treatment of cancer.
However, more in-depth analysis
of all the pathways involved,
for example, in cell proliferation,
growth, and survival,
which can be
due to different mutations
within the same
phenotypic outcome
can highlight all the pathways
and provide potential
therapeutic targets
for this type of cancer.
