exploring the genetic diversity of a canine contagious cancer – university of cambridge
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exploring the genetic diversity of a canine contagious cancer
Adrian Baez-Ortega
Department of Veterinary Medicine Research Afternoon 06/07/2016
Hi. My name is Adrian and I’m a PhD student at the Transmissible Cancer Group of the University of Cambridge. This is a very brief summary of the work that I have done during the first year of my PhD. (However, I’m not including any unpublished results.)
ANNA CZUPRYNA
I’m studying the genetics of a contagious cancer known as Canine Transmissible Venereal Tumour, or CTVT. This is a sexually-transmitted cancer that affects thousands of dogs worldwide.
CTVT is the oldest known living cancer. It first arose in a single dog some 11,000 years ago, and then spread across the global canine population as a venereal parasite.
~11,000 years ago
ANDREA STRAKOVA
As it spread, CTVT acquired different mutations in its DNA. And, in order to understand the natural history of CTVT, and how it became a transmissible cancer, we are studying the genetic diversity provided by these mutations. For that, first we need to read the tumours’ DNA using a technique called whole-exome sequencing.
~11,000 years ago
ANDREA STRAKOVA
This technique only sequences (reads) the parts of the genome that are used for making proteins, called exons. The sum of all the exons is called the exome, which makes up approximately 1% of the whole genome.
UNIVERSITY OF WASHINGTON
We have sequenced the exomes of hundreds of CTVT tumour samples coming from all around the world. My colleague Andrea Strakova has done an incredible job in managing the collection and processing of all our CTVT samples.
Once we have the sequencing data from all these tumours, we need to find out which mutations are present in them. For that, I have developed a computational tool for identifying mutations in transmissible cancer data, called Somatypus.
https://github.com/adrianbaezortega/somatypus
Using this tool, we can identify the mutations present in each tumour sample. And therefore, we can work out the relationship between the tumours by looking at the mutations that they share. This phylogenetic analysis is helping us to understand how CTVT has spread across continents.
However, we want to classify not just the tumours, but also the mutations themselves. We have a set of mutations that we have identified in the exons of the CTVT genome. These mutations are not all the same. They can be classified according to the change they produce in the DNA, and also based on where they occur in the sequence.
THOMAS SPLETTSTOESSER
Once we have categorised the mutations, we can look at the relative frequency of each mutation type. This leads to a mutational profile, or spectrum.
THOMAS SPLETTSTOESSER
By comparing CTVT’s mutational profile to those of different mutational processes that have been described in human cancers (using the COSMIC catalogue), we can determine which processes are responsible for the mutations that we see in tumours coming from different parts of the world.
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http://cancer.sanger.ac.uk/cosmic/signatures
ANNA CZUPRYNA
These data indicate that exposure to ultraviolet light is responsible for many of the mutations in CTVT. This fits the fact that CTVT tumours are frequently exposed to sunlight. Moreover, the cells located near the tumour’s surface, which receive more sunlight, probably have a higher chance of being transmitted to another dog.
In summary, by studying the genetic diversity of CTVT, we aspire to further our understanding of how this unique cancer arose and conquered the world.
TOKYOSHIP
Elizabeth Murchison
Young Mi Kwon
Maire Ni Leathlobhair
Maximilian Stammnitz
Andrea Strakova
Tracy Wang
www.tcg.vet.cam.ac.uk