Shining a light on melanomas that aren't caused by the sun

Shining a light on melanomas that aren't caused by the sun

4 May 2017

‘Slip, slop, slap’ is synonymous with being Australian and playing it safe in the sun. These sun smart rules reduce our chances of getting melanoma of the skin. However, new research tells a different story for those affected by rarer forms of melanoma.

The genetic study, led by Australian researchers at Melanoma Institute Australia, QIMR Berghofer Medical Research Institute and The University of Sydney as part of the Australian Melanoma Genome Project, has found that melanomas on the hands and feet (known as acral) and internal surfaces (known as mucosal) are not linked to ultraviolet (UV) radiation. This is in contrast to melanoma of the skin, which is strongly related to UV radiation.

The research, published today in the prestigious Nature journal, shows that acral and mucosal melanoma have different causes to skin melanoma. This has implications for preventing and treating these forms of melanoma, which occur worldwide.

“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,” says Professor Richard Scolyer, Conjoint Medical Director of Melanoma Institute Australia and a lead author.

Every 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. These forms of melanoma often behave more aggressively, are harder to diagnose and have a poorer outcome compared to skin melanoma.

Treatment for skin melanoma has advanced rapidly in recent years, with therapies tripling the life expectancy of some advanced melanoma patients. For the first time, this research sheds light on why revolutionary treatments—many of which have been pioneered at Melanoma Institute Australia—don’t work as well for acral or mucosal melanomas.

“Acral and mucosal melanomas occur all over the world, but they have been even more challenging to treat than skin melanoma,” says Professor Nicholas Hayward, a lead author from QIMR Berghofer Medical Research Institute. “Knowing these are really different diseases to skin melanoma is important for development of future therapies.”

The study also found acral and mucosal melanomas have much less gene damage compared with skin melanoma and the damage “footprints" did not match those of any known causes of cancer, like sun exposure. This means we must target new research to discover what is causing these cancers, and what can prevent them.

While they had fewer gene drivers that could be targeted for therapy, new ones were found. Some mucosal melanomas unexpectedly had mutations in the SF3B1 and GNAQ genes, which had previously only been connected to melanoma of the eye.

Understanding which gene mutations are driving an individual tumour is the basis of personalised cancer medicine. This is the first study to survey the entire DNA sequence of melanomas, not just the genes themselves, giving 50 times more information than in previous work. Many genes were found to have damage in their control regions, the so-called “dark matter” of our genome, and these may be previously unsuspected drivers of melanoma.

“This is a world-leading genetic analysis of melanoma,” explains Professor Graham Mann, a lead author at Melanoma Institute Australia. “We are working hard now to turn these discoveries about the uniqueness of acral and mucosal melanoma, and about the new control mutations, into better results for our melanoma patients.”

Publication: Hayward, N.K. et al. Whole-genome landscapes of major melanoma subtypes. Nature. 03 May 2017. doi: 10.1038/nature22071. [Epub ahead of print]

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