CANINE CANCER & COMPARATIVE GENOMICS
By Leslie Manis, Health/Genetics Chairman, ASTC
(Published in ASTC Barks, Sept. 2010)
[Every effort has been made to ensure accuracy of information. However,
this is not a substitute for prompt veterinary care. Any similarity
to other publications is unintentional. Published
online at Sealyhealthguard.org, 7/20/11]
Download PDF version
At the AKC-CHF Parent Club Health Conference in 2010, I was pleased
to attend a presentation by the world-renowned cancer
researcher Dr. Matthew Breen. Dr. Breen completed his
PhD in cytogenetics (a branch of genetics which focuses
on the structure & function
of the cell, especially the chromosomes) then spent
two years as a Post Doc in molecular genetics.
developed molecular cytogenetics reagents, resources
and techniques for use in canine genome mapping, comparative
cytogenetics and cancer studies. He is the Treasurer
for the Canine Comparative Oncology & Genomics
Consortium (CCOGC) sponsored by the AKC-CHF and the
Morris Animal Foundation. Dr. Breen currently has a
number of active grants from the CHF that are focused
on the molecular cytogenetic evaluation of canine tumors.
The CCOGC is a collaboration of veterinary and medical oncologists,
pathologists, surgeons, geneticists & molecular & cellular
biologists. This group determined that a well-described repository
of tissues (tumor and normal) from tumor-bearing dogs was an essential
resource needed for advancing our understanding of canine cancer.
The biospecimen repository, sponsored by Pfizer, houses tumor tissue,
normal tissues, serum, plasma, peripheral blood mononuclear cell preparations,
genomic DNA, RNA and urine samples. [In June of last year (2009),
the FDA approved PfIzer's Palladia, and anti-cancer drug for dogs.
Palladia is for treating recurrent cutaneous mast cell tumors. It
prevents formation of new blood vessels in tumors.] The goal of the
CCOGC is to obtain 3,000 samples of lymphoma, osteosarcoma, melanoma,
hemangiosarcoma, soft tissue sarcoma/histiocytic sarcoma, mast cell
tumors and lung cancer.
Advances in genomics technologies over the past decade have been
New forms of sequencing technology have made the process much faster & less
expensive. Comparative genomics is the comparison of the sequence
and function of the genomes (a genome includes all the genes of a
species) of different species, such as the human & the dog. Since
both genomes (human & dog) have been mapped, scientists like Matthew
Breen can identify regions of both genomes that are shared and that
are associated with disease and determine which genes are playing
key roles in a variety of disease processes. They have already found
that specific genetic changes are associated significantly with subtypes
of canine cancers and have also identified genetic changes that are
associated strongly with response to routine therapy.
This information can one day be used to more accurately predict the
prognosis and survival time of canine cancer patients.
Currently, the inability to accurately predict response to treatment
and survival time is the major reason (in addition to cost) many owners
decide not to treat their dogs.
While the CCOGC is building its collection of biospecimens (thanks
to the help of hundreds of dog owners), scientists have generated
a series of sophisticated molecular cytogenetic reagents and resources
that provide a way to examine each tumor specimen for genetic changes
that are associated with the corresponding malignancy.
Using these new tools, they have evaluated the tumor genomes of over
500 canine cancer patients. For each cancer type studied, they have
demonstrated the presence of numerous cytogenetic signatures that
are associated with cancer subtypes and that also correspond to those
in humans. If these are so similar, there's a good chance that human-derived
therapies will be effective in canine oncology.
As they study these genomic changes, they can begin to determine
which are associated with the disease process and which are secondary
effects of tumor-associated genomic instability. They are well on
their way toward development of more sophisticated molecular sub-classification
of canine cancers, a process that should facilitate the emergence
of tailored therapies.
Accessibility to new information is becoming easier and faster, and
the demands of the public for the latest veterinary care are increasing.
It is conceivable that, as with human health, the next decade may
bring genotyping and/or whole genome sequencing/analysis of dogs for
the purposes of health management.