Genetic mutation leads to tumor regression in Tasmanian devils

Scientists at Washington State University have discovered genes and other genetic variations that appear to be involved in the reduction of cancerous tumors in Tasmanian devils.

Their research is an important first step toward understanding the cause of diabolical facial tumor disease, a form of near-fatal and contagious cancer, in a small percentage of Tasmanian devils and could have implications for cancer treatment in the United States. man and other mammals. as well as.

"Some of the genes we think have a role in the regression of tumors in Tasmanian demons are also shared by humans," said Mark Margres, a former WSU postdoctoral fellow today at the University. Clemson. "Although we are still at a very early stage, this research could potentially contribute to the development of tumor regression-inducing drugs in devils, humans, and other mammals that do not have this genetic variation. necessary."

Devils in the process of disappearing

The Tasmanian devils have been threatened with extinction by the rapid spread of devil's facial tumor disease, one of only four known forms of transmissible cancer and by far the most lethal. Since it's been documented for the first time in 1996, the disease has eliminated about 80% of the demons in Tasmania, the only place in the world where animals live.

Margres is part of an international team of researchers on devil facial tumor disease led by Andrew Storfer, an evolutionary geneticist and biology professor at WSU.

Over the last decade, the Storfer team has been studying how some Tasmanian devil populations develop genetic resistance to devil's facial tumor disease, which could help the species to avoid extinction.

A year ago, Storfer's Australian collaborators Manuel Ruiz, Rodrigo Hamede and Menna Jones noticed something very unusual about trapping and tagging devils in an isolated area of ​​Tasmania. A very small number of devils who have developed facial tumors have not died. Rather, over a period of several months, the tumors left alone.

"It was very unusual and we wanted to look for evidence of genomic variation that spontaneously caused the improvement of these demons," Storfer said.

The researchers sequenced the genomes of seven Tasmanian devils that underwent tumor regression and three others.

They discovered that devils who had lost their tumor had three highly differentiated genomic regions containing several genes known to be linked to the immune response and cancer risk in humans and other mammals.

"We have identified some candidate genes that we think are important in the tumor regression response and we can now begin to functionally test them to see if it is possible to obtain the same tumor regression response," he said. declared Margres. "While it is difficult to say anything specific with such a small sample, I think this research is somehow the first step towards characterizing the genetic basis of the tumor regression trait."

The results of the work of Margres and Storfer were published last month in the journal Genome biology and evolution. The researchers said the next step in the research was to analyze the tumor genome to determine if there were specific mechanisms or mutations leading to the narrowing of the tumor.

Discovery of tumor regression mechanisms

Tumor regression is not a phenomenon exclusive to Tasmanian demons. Although extremely rare, it has been documented in human cancers.

One of these cancers is Merkel cell carcinoma, a rare type of skin cancer that often appears on the face, head, or neck.

The doctors observed a spontaneous regression of the tumor in a patient with Merkel cell carcinoma for the first time in 1986 and this has occurred at least 22 times since. However, researchers remain uncertain about the cause of spontaneous disappearance of tumors.

Storfer and Margres hope that the development of a better understanding of the genetic basis of tumor regression in Tasmanian devils may eventually allow the identification of general mechanisms underlying tumor regression of Merkel cell carcinoma. and other human cancers.

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More information:
Mark J Margres et al, The genomic basis of tumor regression in Tasmanian devils (Sarcophilus harrisii), Genome biology and evolution (2018). DOI: 10.1093 / gbe / evy229