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Rare and deadly melanomas not caused by the sun

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Two rare and deadly forms of melanoma are not caused by sun exposure new genetic research led by Australian researchers reveals today.

Published in Nature, the study shows that acral melanomas found on the palms, soles of the feet and under the nails, and mucosal melanomas found on the body’s internal surfaces, are not linked to ultraviolet (UV) radiation.

This is in contrast to melanoma of the skin, which is strongly related to UV radiation. This finding has implications for preventing and treating these forms of melanoma, which occur worldwide.

The genetic study involved researchers from 20 institutions around the world and was led by researchers at the University of Sydney, Melanoma Institute Australia, and QIMR Berghofer Medical Research Institute and as part of the Australian Melanoma Genome Project.

It is the first study to survey the entire DNA sequence of melanomas, not just the genes themselves, and provides 50 times more information than previous analyses of these cancers.

Each year in Australia, up to 420 people are diagnosed with acral or mucosal melanomas. They affect people of all ethnic backgrounds, and are the most common forms of melanoma in people with very dark skin.

They often behave more aggressively, are harder to diagnose, and have poorer outcomes than the more common UV-caused skin melanomas.

Treatment for skin melanomas has advanced rapidly in recent years, with therapies tripling the life expectancy of some advanced melanoma patients.

This new study sheds light on why treatments for skin melanomas don’t work as well for acral or mucosal melanomas.

“This is a world-leading genetic analysis of melanoma,” said cancer geneticist and senior author Professor Graham Mann.

“We are working hard now to turn these discoveries about the uniqueness of acral and mucosal melanoma into better results for melanoma patients.” Professor Mann Chairs the University of Sydney’s Cancer Research Network and Melanoma Institute Australia’s Research Committee.

The study also found that acral and mucosal melanomas have less gene damage than skin melanoma and that their damage “footprints” didn’t match those of any known causes of cancer, such as sun exposure. This means researchers will need to do more work to discover what causes these cancers, and what can prevent them.

Although acral and mucosal melanomas have fewer gene drivers that can be targeted for therapy, new ones were found. For example, some mucosal melanomas had mutations in the SF3B1 and GNAQ genes, which has previously been observed only in melanoma of the eye.

Understanding which gene mutations are driving an individual tumour is the basis of personalised cancer medicine.

Many genes were found to have damage in their control regions, the so-called “dark matter” of the genome, and these may be previously unsuspected drivers of melanoma.

“This is by far the largest study to have looked at the whole genome in melanoma, and it has proven these less common melanomas are strikingly different in terms of their causes,” said University of Sydney’s Professor Richard Scolyer who is Conjoint Medical Director of Melanoma Institute Australia and a lead author of the paper.

(Source: University of Sydney, Nature)

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Posted On: 3 June, 2017
Modified On: 2 June, 2017


Created by: myVMC