Genetic mutation drives tumor regression in Tasmanian devils

Genes and other genetic variations that appear to be involved in cancerous tumors shrinking in Tasmanian devils have been discovered by Washington State University scientists.
The research is an important first step toward understanding what is causing devil facial tumor disease — a nearly 100 percent fatal and contagious form of cancer — to go away in a small percentage of Tasmanian devils. Indirectly, it could have implications for treating cancer in humans and other mammals as well.
“Some of the genes we think have a role in tumor regression in Tasmanian devils are also shared by humans,” said Mark Margres, a former WSU postdoctoral researcher now at Clemson University. “While still in a very early stage, this research could eventually help in the development of drugs that elicit the tumor regression response in devils, humans and other mammals that don’t have this necessary genetic variation.”

Disappearing devils

Tasmanian devils have been pushed to the brink of extinction by the rapid spread of devil facial tumor disease, one of only four known forms of transmissible cancer and by far the deadliest. Since it was first documented in 1996, the disease has wiped out an estimated 80 percent of devils in Tasmania, the only place in the world where the animals live.
Margres is part of an international team of researchers studying devil facial tumor disease that is led by Andrew Storfer, an evolutionary geneticist and WSU professor of biology.
For the last decade, Storfer’s team has been investigating how some Tasmanian devil populations are evolving genetic resistance to devil facial tumor disease that could help the species avoid extinction.
A year ago, Storfer’s Australian collaborators, Manuel Ruiz, Rodrigo Hamede and Menna Jones noticed something very unusual while trapping and tagging devils in an isolated region of Tasmania. A very small number of devils that developed facial tumors did not die. Rather, over a period of several months, the tumors went away on their own.
“This was very unusual and we wanted to test for evidence of genomic variation that was causing these devils to spontaneously get better” Storfer said.

The researchers sequenced the genomes of seven of the Tasmanian devils that underwent tumor regression and three that did not.
They found the devils that lost their tumors had three highly differentiated genomic regions containing multiple genes that are known to be related to immune response and cancer risk in humans and other mammals.
“We identified some candidate genes that we think may be important in the tumor regression response and now we can begin to functionally test these genes to see if it is possible to elicit the same tumor regression response,” Margres said. “While it is hard to say anything definite with such a small sample size, I think this research is sort of the first step towards characterizing the genetic basis of the tumor regression trait.”
The results of Margres and Storfer’s work were published last month in the journal Genome Biology and Evolution. The researchers said the next step in the research is to analyze the tumor genome to see if there are specific mechanisms or mutations there that lead to tumor shrinkage.

Uncovering mechanisms of tumor regression

Tumor regression is not a phenomenon exclusive to Tasmanian devils. While extremely rare, it has been documented in human cancers.
One such cancer is Merkel Cell Carcinoma, a rare type of skin cancer that often appears on the face, head or neck.
Doctors observed spontaneous tumor regression in a Merkel Cell Carcinoma patient for the first time in 1986 and it has occurred at least 22 times since. However, researchers remain unsure of what causes the tumors to go away on their own.
Storfer and Margres hope is that developing a better understanding of the genetic basis of tumor regression in Tasmanian devils may eventually enable the identification of general mechanisms underlying tumor regression in Merkel Cell Carcinoma and other human cancers.
This research was funded by the National Institutes of Health (R01‑GM126563), the National Science Foundation (DEB 1316549), and the Australian Research Council (FT100100250).

Top photo: Tasmanian devils are the largest carnivorous marsupials in the world.

By Will Ferguson for WSU Insider

“Endangered Butterflies as a Model System for Managing Source-Sink Dynamics on Department of Defense Lands”

SERDP 2018 Project of the Year Award for Resource Conservation and Resiliency!

SERDP 2018 Project of the Year Award for Resource Conservation and Resiliency

Project Team

• Dr. Elizabeth E. Crone – Tufts University
• Dr. Cheryl B. Schultz – Washington State University
• Dr. Nick M. Haddad – Michigan State University
• Dr. William F. Morris – Duke University
• Dr. Brian R. Hudgens – Institute for Wildlife Studies
• Dr. Christine C. Damiani – Institute for Wildlife Studies
• Dr. Norah Warchola – Tufts University

By: Hailey Meyer

Madison Armstrong has spent much of her time experiencing the world through research and scientific exploration. To say that she has been involved in an abundance of research experiences, would be a massive understatement.

Armstrong is a senior in the WSU Honor’s College, studying Evolutionary Biology and Ecology, with a minor in Genetics and Cell Biology.

Armstrong started her research experience in Ecuador at age 17, working for “Operation Wallacea,” a conservation company that is based out of the United Kingdom. She met scientists from all over the world that had the same interests and questions that she had. This is where her curiosity and concern for biology started.

“I realized that biology could be more than just a favorite class, a job or an interesting topic,” she explained, “it is critical for the success of the planet,” Armstrong said.

When she first came to WSU in 2015, she continued to fuel her curiosity by joining Dr. Dybdahl’s lab that focused on clonal population spread. Armstrong began identifying dispersals of clonal lineages of the aquatic New Zealand mud snail. By identifying favorable environmental conditions of clonal types, she found that human dispersal played a large role in the spread of this invasive species. In just her first year here at WSU, Armstrong presented at the 2016 WSU Symposium for Undergraduate Research and Creative Activities (SURCA).

Armstrong has also conducted research that focused on phenotypic plasticity of the shell shape in the New Zealand mud snail. She observed that the variation in shell shape occurred across populations of the same clonal type, US1, even though no genetic variation was present.

After about a year of research, Armstrong collected data that supported her hypothesis that plasticity played a role in shell shape, which affected snail movement in a self-made flow system. She was awarded 2^nd place for her research poster at SURCA in 2017, and attended the National Society for the Study of Evolution Conference in Portland, OR to present her research poster. She then presented at SURCA the following year, and this time was awarded 1^st place. Armstrong was also recognized for an exceptional research poster at a local Evolutionary Biology Conference of the Pacific Northwest region.

This past summer, Armstrong attended an intensive week-long computational Bioinformatics course hosted by Physalia in Berlin. She was able to work hands-on with datasets provided from scientists from around the world, and represented the U.S. as the only American in the course.

“My research experiences at WSU have enabled me to gain the necessary skills for graduate school and future research opportunities,” Armstrong says. “I constantly strive to inspire others to pursue their interests, which has led to involvement in a large variety of programs.”

Armstrong thanks SBS and CAS for providing her with funding to conduct research projects for the past four years, and is extremely grateful to have been given the opportunity to pursue her own research questions as an undergraduate student.