Using DNA sequencing, researchers in the UK have discovered possible new treatment targets for a rare form of cancer known as mucosal melanoma. The more we know of the sub-types of melanoma, the more we can tailor treatment for patients and improve their prospects, says Cancer Research UK, a core sponsor of the center where the research took place.

In a statement that describes the find as a “molecular bullseye” for targeted treatment opportunities, lead author Richard Marais, a professor at the Paterson Institute for Cancer Research at the University of Manchester, says their discovery reveals the genetic fingerprint of mucosal melanoma is completely different from its more common counterpart, cutaneous or melanoma skin cancer.

“There’s no classic UV signature, which reinforces our thoughts that this type of cancer isn’t linked to the sun and sunbeds and suggests that these types of melanoma start in different ways,” says Marais.

Nic Jones, chief scientist at Cancer Research UK, who provide the core funding for The Paterson Institute, says the discovery suggests the two types of melanoma are more like two different diseases that just happen to affect the same cells.

“Cutaneous melanoma is strongly linked to UV exposure, number of moles, family history and ethnicity, while mucosal melanoma doesn’t seem to be linked to these factors. But it’s usually more aggressive and more likely to spread to other parts of the body than cutaneous melanoma,” he explains.

A report on the findings appears in an online first issue of The Journal of Pathology published on 7 June.

Melanoma is a cancer of melanocytes, the pigment-producing cells of the body that give skin its colour. Cutaneous or melanoma skin cancer is the most common form of melanoma.

But there are also rarer forms of melanoma that arise from melanocytes located elsewhere, such as in the eye (ocular melanoma) and the mucosal surfaces that line the sinuses, nasal passages, mouth, vagina, anus, and other parts of the body (mucosal melanoma).

Around 120 to 130 cases of mucosal melanoma are diagnosed each year in the UK, compared with around 12,000 cases of cutaneous melanoma.

While we already know ultra-violet (UV) radiation is a risk factor for cutaneous melanoma, we know little about the likely causes of mucosal melanoma. So there are no treatments for this rare cancer, and the 5-year survival rates are only around 40% compared with more than 90% for the cutaneous form.

Selumetinib, an experimental drug developed by AstraZeneca, is the first targeted medication to show a significant clinical benefit for patients with melanoma of the eye, a recent study reports.

Marais and colleagues have revealed for the first time the genetic faults that occur in mucosal melanoma.

For their study they used “whole genome and whole exome sequencing” to look at mutations in the genomes of ten mucosal melanomas.

They noticed mutation rates were considerably lower than those that occur in sun-exposed cutaneous melanoma, but comparable to rates seen in cancers not linked to exposure to known triggers of mutations.

“In particular, the mutation signatures are not indicative of ultraviolet light- or tobacco smoke-induced DNA damage,” they note.

They did, however, find some of the genes mutated in mucosal melanoma were the same as those reported for other cancers.

And they saw far more other types of genetic alterations, such as copy number and structural variations, in mucosal melanoma than have been seen in cutaneous melanoma.

They conclude that “mucosal and cutaneous melanomas are distinct diseases with discrete genetic features” and that the findings suggest they arise from different mechanisms, and that structural variations play a bigger role in the development of mucosal melanoma than they do in the development of cutaneous melanoma.

Marais says the discovery means they can now look at these genetic faults and start to develop “desperately needed targeted treatments” for this rare type of melanoma.

“It’s exactly this type of vital research that we and other scientists will be doing at the new Manchester Cancer Research Centre – bringing together a wide range of expertise to revolutionise cancer treatment,” he adds.

Jones says:

“Research like this is helping us to better understand how this disease works and is the first step towards developing more effective treatments. By recognising the differences between sub-types of melanoma, we will be able to tailor treatment for patients so they have the best chance of beating the disease.”

Funds from The Catalyst Club, a group of philanthropists who have invested in a range of cancer research projects, helped finance the study. The Club is raising £10m towards personalized cancer treatment.

US researchers recently reported in the April 2013 issue of Molecular Cancer Therapeutics how for the first time, using lab tests on cell cultures and mice, they showed that gossypin, a naturally-occurring substance found in plants, may be an effective treatment against cutaneous melanoma.

Written by Catharine Paddock PhD