Wednesday , January 27 2021

Cancer comparison across species highlights new drug targets

Cancer genes in mucosal melanoma, a rare and poorly understood sub-type of melanoma, have been compared for the first time in humans, dogs and horses by researchers at the Wellcome Sanger Institute and their partners. Scientists sequenced the genomes of the same cancer across different species into pin-point key cancer genes.

The results reported in nature Communications, provide insight into how cancer develops over the tree of life and be able to lead the development of new therapies.

Mucosal melanoma is a rare form of melanoma, a type of tumor that is usually associated with skin cancer. Of the 15,400 people diagnosed with melanoma in the UK each year *, about 1 percent will be diagnosed with mucosal melanoma.

The cancer originates from the cells that produce pigment, known as melanocytes, which are not only found in the skin, but also mucosal surfaces in the body, such as sinuses, nasal passages, mouth, vagina and anus.

The risk factors for mucosal melanoma are unknown, and there is no known link to UV exposure or family history. Patients with cancer often occurring late in the progress of the disease and the primary treatment for mucosal melanoma are surgical removal of the tumor. In addition to humans, cancer affects dogs and horses with varying results for the different species.

To uncover the genetics supporting the cancer, researchers at the Sanger Institute and their partners sequenced the genomes of mucosal melanoma tumors taken from humans, dogs, and horse patients who had been diagnosed with the disease.

Analyzing the genomic data from 46 human, 65 dogs and 28 horse melanoma tumors, all at the primary stage of cancer, scientists revealed a handful of genes mutated in all species.

Dr. David Adams, similar author of the Wellcome Sanger Institute, said: "Genomics gives us a unique view of the hidden similarities and differences in cancer between species. The genetic changes or mutations we found in mucosal tumors in humans, dogs and horses suggest that They are important enough to be conserved between species. These key mutations are likely to drive the cancer and could be the target of new drug development. "

Immunotherapy, the stimulation of the body's own immune system to attack cancer cells, has been used to treat some people with melanoma, but has not been effective for humans with subtype, mucosal melanoma, and the cause was unknown. Researchers now suggest that contrast to skin melanoma carries mucosal melanoma tumors a few mutations so that they remain "hidden" to the immune system and do not spark the immune response needed to target the cancer.

Kim Wong, first author of the Wellcome Sanger Institute, said: "Understanding the genetic changes that support mucosal melanoma suggests why people with this type of cancer cannot benefit from immunotherapies. Genomics can help identify who is greater risk of developing mucosal melanoma and providing information to genetic counselors and doctors who advise patients on disease management. "

This study is the first to sequence horse tumors and the first genomic experiment of this scale on canine tumors. Gray horses are genetically susceptible to getting melanoma. Cancer, however, is very different in horses, as it usually does not spread, unlike the disease in humans and dogs.

Professor Geoffrey Wood of the University of Guelph in Canada said: "Spontaneous tumors in dogs are recognized as" models "of human cancers for the development of therapies that can benefit both species. This study shows the importance of understanding the genetic similarities and differences in cancer across species so that the most biologically relevant drug targets are prioritized. "


Notes for editors:

* Https: // /cancer /melanoma /about

Learn more about mucosal melanoma: https: // /understand-melanoma /what-is-melanoma /mucosal melanoma


Kim Wong et al. (2019) Combination of genomic ligand comparison of human mucosal melanoma with canine oral and equine melanoma. nature Communications. DOI: 10,1038 / s41467-018-08081-1


This study was supported by Wellcome, Cancer Research UK and the European Research Council under the European Union Seventh Framework Program (FP7 / 2007-2013) / ERC Synergy Assistance Agreement (319661 COMBATCANCER).

Selected websites:

About the University of Guelph

The University of Guelph is one of Canada's best comprehensive and research-intensive universities. The University of Guelph is recognized as Canada's Food University and renowned for excellence and innovation across physical and life sciences, business economics, social sciences and agricultural and veterinary fields. Uh G has exciting urban hubs and rural communities, and has nearly 30,000 undergraduate and graduate students on campus in Guelph, Toronto and Ridgetown, including 1,200 international students from more than 100 countries. Under our "mainstream" approach to teaching and learning, we strive to develop future leaders who have creative and critical capabilities to face challenges and seize opportunities in our increasingly complex and interconnected world.

Wellcome Sanger Institute

Wellcome Sanger Institute is one of the world's leading genomic centers. Through its ability to conduct research on a scale, it is able to engage in courageous and long-term exploration projects designed to influence and strengthen medical science globally. Institute research results generated through own research programs and through its leading role in international consortia are used to develop new diagnostics and treatments for human disease. To celebrate its 25th year in 2018, the Institute sequences 25 new species of species in the UK. Learn more at http: // or follow @sangerinstitute

About Wellcome

Wellcome exists to improve health by helping good ideas to thrive. We support researchers, we address major health challenges, we fight for better science, and we all help to get involved in science and health research. We are a politically and financially independent foundation.

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