Study finds new clues in eye cancer

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About five per cent of melanomas in the eye are caused by exposure to sunlight, while the majority are not, a new study by QIMR Berghofer and Queensland Ocular Oncology Service has found.

The findings indicate this cancer – uveal melanoma – is made up of a number of subclasses and could explain why it is difficult to treat.

Uveal melanoma (also known as eye or ocular melanoma) is relatively rare. About 175 new cases are diagnosed in Australia annually.

Many patients will lose an eye or sight as part of their treatment, and the cancer will spread to other parts of the body for almost half the patients.

Co-lead author and head of QIMR Berghofer’s Oncogenomics group, Professor Nick Hayward, said the researchers also discovered that a common anti-cancer gene, named TP53, was often switched off in uveal melanoma.

“We hadn’t known the role of the TP53 gene in uveal melanoma before this study, so our findings open up new avenues for potential treatments for this disease,” Professor Hayward said.

“Identifying that this anti-cancer gene is turned off in some uveal melanomas improves our understanding of how the tumours develop and may provide a target for new treatments.”

The researchers sequenced the entire genomes of more than 100 patients with uveal melanoma and compared the data on DNA mutations with their health outcomes.

Co-lead author, ophthalmologist and Director of Queensland Ocular Oncology Service, Associate Professor Bill Glasson, said uveal melanoma was hard to treat, particularly when it metastasised.

“Understanding that uveal melanoma is made up of a number of mutational subclasses explains why patients respond so differently to treatments,” Associate Professor Glasson said.

“We found that tumours in the iris have more mutations, which means they are potentially more suitable for immunotherapy since a high number of mutations has been shown to be a marker of response to immunotherapy in the treatment of metastatic skin melanomas.”

Joint first author and QIMR Berghofer researcher, Dr Peter Johansson, said the study looked at the total number and patterns of mutations to see if there were clues to how some of the tumours may have developed.

“We wanted to identify mutations in uveal melanomas that could be targeted with drugs and other treatments because the disease is highly resistant to current therapies,” he said.

“The study indicated the larger number of gene mutations in iris melanoma was predominantly caused by sunlight exposure. In contrast, there is no indication that sunlight plays a part in the majority of uveal melanomas which occur in the back of the eye.”

Dr Kelly Brooks, a researcher at QIMR Berghofer and joint first author of the study, said the findings added further weight to current general sun protection advice.

“This study confirms wearing sunglasses could help prevent up to five per cent of uveal melanoma cases,” she said.

“We now really need to turn our attention to better understand the details of how uveal melanoma develop, which will hopefully lead to new suitable drug targets for the other subclasses of uveal melanoma which make up 95 per cent of the disease.”

The study results have been published in the journal Nature Communications.

The work was partly funded by the Walking on Sunshine Foundation. One of its founders, Anne Stanton, passed away last year from uveal melanoma.

 
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