Rare gene mutations associated with oculocutaneous albinism (OCA) increase the risk of both amelanotic and hypomelanotic melanomas (AHM) and pigmented melanomas, Australian research shows.

A Queensland-led study compared exome sequencing on saliva samples from 28 people with AHM, 303 with pigmented melanoma and 1,144 Australian controls.

The study, published in PLOS ONE, found deleterious variants in TYR/OCA1 associated with albinism were significantly more common in the AHM cases than in the pigmented melanoma cases.

Rare TYR variants were at a minor allele frequency of 4.67% in AHM cases compared to 1.76% in the pigmented melanoma cases, and 1.14% in the controls (p =0.0088).

And the same was true for the OCA2 hypomorphic allele p.V443I.

“The OCA2 hypomorphic allele p.V443I was also more common in melanoma cases than controls (1.8% v 1.0%; P =0.02), and more so in amelanotic/hypomelanotic melanoma (4.4%; p =0.007),” the study authors said.

“We suggest that somatic loss of function at these loci could contribute to the loss of tumour pigmentation, consistent with this we found a higher rate of somatic mutation in TYR / OCA2 in amelanotic/hypomelanotic melanoma vs pigmented melanoma samples (28.6% vs 3.0%; P =0.021) from The Cancer Genome Atlas Skin Cutaneous Melanoma collection,” they wrote.

The study also found that while most of the AHM patients had fair skin, some had moderate skin complexions.

“Therefore, AHM does arise on constitutively pigmented skin types, and tumour colour can vary within the same patient.”

Lead author Dr Jenna Rayner, from the Dermatology Research Centre at the University of Queensland, told the limbic that up to about 8% of melanomas can be hypomelanotic or hypopigmented.

“And these melanomas are really scary for patients but they really scare doctors and dermatologists as well. And that’s because they are very easily missed and often look like benign things like a wart or a scar or a pimple.”

As a consequence they were often detected later and patients were having treatment at a more advanced stage of disease.

“What we hypothesised, was whether some of the genes that play a role in albinism could have a role in these melanomas which are skin-coloured or pale.”

“And what we found was that people who have these hypopigmented melanomas are more likely to have one of these gene mutations associated with albinism. These variants can play a role … the suggestion was the loss of function at these loci contributes to loss of tumour pigmentation.”

Dr Ryaner, a dermatology trainee, said the next step was to look at tissue samples from these rare melanomas with the potential of genetic risk profiling in the future.

“In a population such as Australia or Queensland, where melanoma is so common, this may be a type of testing that can be done to personalise people’s cancer risk.”