Mucosal Melanoma Treatment Targets Found with DNA Sequencing

“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.

Melanoma, a Cancer of Melonocytes

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.

Genetic Faults Behind Mucosal Melanoma Revealed for the First Time

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.

Findings Should Help Develop Tailored Treatments for Melanoma

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