Saturday, August 10, 2019

A Study in the Evolution of a Transmissible Cancer

There is a canine-related cancer that is sexually transmitted from one animal to another. It is the canine transmissible venereal tumor (CTVT) that presents as genital tumors. It has been shown that this cancer spreads through the transfer of living cancer cells (see image below) through coitus. These CTVT cells function as a unicellular, asexually reproducing (but sexually transmitted) pathogen. In addition, CTVT cells are genetically aberrant in terms of chromosome number – studies have established that instead of the normal 78 chromosomes present in the canine species these cells have a chromosome number in the range of 57-64. This type of cancer represents an exceedingly rare etiology in that the cancer is spread through the transfer of the cancer cell itself.

CTVT Cells
This disease exists worldwide and apparently has the longest known and most prolific evolutionary lineage. This reality provides an opportunity to explore the mechanism of the evolution of cancer over the long term. For this reason, Adrian Baez Ortega, a bioinformatician, and her colleagues from the Transmissible Cancer Group at Cambridge University, UK, have done a detailed analysis of genetic sequence data from 546 individual CTVT tumors taken from diseased animals. Their focus in this analysis was to identify somatic single-nucleotide variants (SNVs) from the exomes – areas of the genetic material that are involved in the active production of proteins. The aim of this intense research study was to help to uncover the mutational events and genetic signatures of the evolutionary selection process over the thousands of years.

One of the predominant findings of this analysis was that this lineage arose from its originator canine individual between 4000 and 8500 years ago most likely from Asia with the most recent ancestor of the current global distribution estimated to have lived about 1900 years ago. There does not appear to be any positive selection for this lineage. In addition, the author of this study concludes that, “a highly context-specific mutational pattern named signature A was identified, which was active in the past but ceased to operate about 1000 years ago. BP, years before present.”

These results provide an insight into the progression of an unusual type of cancer that is transmissible through the transfer of the cancer cell itself rather than through a vector such as a virus – human T Cell Leukemia being one particular example. It also is a demonstration of the power of the widely used tools of research regarding the discovery of the underlying genetic mechanisms involved in disease processes.

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