Spotlight: Oncology
Man and his best friend walk side by side on the path to
improved cancer prognosis
Matthew Breen PhD CBiol FSB,
Molecular Biomedical Sciences, College of Veterinary Medicine
The application of genomics to canine biomedical
research has resulted in significant advances as we
strive to enhance the health and welfare of our
companions. Over the past 10 years we have recruited
tumor tissues and blood samples from hundreds of dogs
presenting with a variety of common cancers. During the
same period we generated a series of sophisticated
molecular cytogenetic reagents and resources that
complete the genomics ‘toolbox’. Collectively these tools
provide a robust means to interrogate tumor specimens
for organizational changes to the genome, which lead to
identification of genomic regions, and ultimately genes,
associated with cancer.
Using genome-wide
analysis of hundreds
of canine tumors we
have demonstrated
the presence of
cytogenetic
signatures
associated with
cancer subtypes and
are now using these
to develop more
sophisticated
approaches to tumor
diagnosis. In
addition we have
begun to define
genomic changes in
tumors that correlate
with prognosis. For
example, in our work with canine lymphoma we
identified numerous regions of the canine genome that
are subject to recurrent copy number changes in the
cancer cells. Evaluation of these observations indicated
that the copy number status of select regions is
associated with the duration of first remission in canine
lymphoma patients treated with standard of care
doxorubicin-based chemotherapy. These data have
been validated in an independent study population and
used to develop a cytogenetic test to predict how long
dogs diagnosed with lymphoma will respond to
doxorubicin-based therapy. This test, which is the first
cancer-associated cytogenetic test in veterinary
medicine, will be available in 2012.
We have demonstrated previously that the chromosome
changes we observe in several canine cancers are
shared with the corresponding cancers in humans. This
provides strong evidence for a shared pathogenetic
origin of several cancers affecting both human and dog.
Analysis of our data has revealed that we are well on
the way towards development of more sophisticated
molecular sub-classification of canine, and possibly
human, cancers. This approach should facilitate the
emergence of improved and tailored therapies for both
species. For example, using our canine lymphoma
prognostic data, we have translated the canine regions
to corresponding regions of the human genome, and
now are evaluating their prognostic significance in a
cohort of human lymphoma patients treated with
doxorubicin-based therapy. Further, the comparative
value of considering genomic changes in both canine
and human cancers is accelerating the process of gene
discovery; by focusing on the shared regions of genomic
alteration we are able to reduce the number of key
genes from lists of hundreds to just a few.
The keys to unlocking some of nature’s most intriguing
puzzles about cancers may be found in the genome of
the dog. Finding such keys in the dog will also lead to
improved understanding of human cancers. For 15,000
years the dog has been man’s best friend. In the 21st
Century it is becoming increasingly evident that the dog
is also man’s best biomedical friend.