Whole-genome sequencing uncovers new skin cancer gene

In collaboration with the Press Association

US scientists have used high-tech DNA sequencing to uncover a new gene linked to melanoma – the most serious form of skin cancer.

The link between the PREX2 gene and melanoma was identified by scientists from the Broad Institute and Dana-Farber Cancer Institute, in a study published in the journal Nature.

They found that PREX2 was damaged in tumour samples from 44 per cent of 25 melanoma patients involved in the study.

The scientists sequenced the whole genomes - the complete set of DNA in a cell – in tumour samples from the patients, and also sequenced the DNA in samples of their blood, as a reference.

By comparing the tumours’ DNA to the ‘normal’ DNA in the blood, the researchers showed that the degree of genetic damage in tumours’ DNA was greatest in patients who had been in the sun most, confirming that chronic sun exposure has a major role in skin cancer.

They also confirmed the importance of faults in two other genes - BRAF and NRAS - in melanoma. These genes, known to be important in sending cell growth signals, and previously linked to melanoma, were damaged in 24 of the 25 tumours studied.

But significantly, PREX2 was also altered in many of the samples.

When looking at PREX2 in a further 107 tumour samples, the researchers found 14 per cent of them contained the altered gene.
Faults in PREX2 have been previously associated with breast cancer.

Mouse experiments suggested that PREX2 mutations spurred tumour growth in ways yet to be determined.

"We still can't say we know exactly how it works," Dr Levi Garraway, senior author, said. "PREX2 may be in a very interesting new category of mutated cancer genes that point us to at least one and maybe more pathways that would be worth targeting therapeutically in melanoma," he added.

Professor Mark Middleton, director of Cancer Research UK’s Experimental Cancer Medicine Centre at the University of Oxford, said: “After the recent success of drugs targeting the faulty BRAF gene in melanoma, we’re very keen to find other genetic mutations that are important in its growth. This research increases our understanding of the disease, the most deadly form of skin cancer, and suggests new ways to treat it.”

The discovery that BRAF mutations are common in melanoma directly led to the development of a drug, vemurafenib, to target these mutations. The drug is currently being assessed by NICE.

Professor Middleton asaid the study also highlighted the important role played by sun damage in melanoma, and emphasises the need to follow simple measures to enjoy the sun safely.

He advised people to use a combination of shade, clothes and SPF 15 sunscreen to protect their skin in strong sunlight.

Copyright Press Association 2012

References

  • Berger, M. et al (2012). Melanoma genome sequencing reveals frequent PREX2 mutations Nature DOI: 10.1038/nature11071