Understanding the genes involved in the development of early brain metastases.

Researchers at Melanoma Institute Australia have identified the genes involved in the type of melanoma that spreads early on to the brain.

A primary melanoma of the skin that spreads to the brain (known as metastasis) typically occurs late in the disease process once melanoma has spread to other parts of the body first, like the liver, bones or lungs. They also usually arise from patients who have thick primary tumours.

However, for about 1 in 5 of patients with brain metastases, the first distant location their melanoma spreads to is the brain. Suprisingly, these patients usually had thin and non-ulcerated primary melanomas – characteristics that would typically give them a more favourable prognosis.

Early detection of melanoma in the brain is critical as treatment is more effective when lesions are small and before symptoms, like seizures and paralysis, have begun. Being able to identify early on which patients are more likely to get brain metastases could be life-saving.

Observations of tumours that develop ‘early brain metastases’ suggest that they could have distinct biological properties, and therefore our researchers were keen to work out which genes in the melanoma, not the person with melanoma, are involved.

In a recent publication, we found that patients who develop early brain metastases tend to have many gene mutations in their melanoma, and in particular, mutations to a gene called KRAS. Very little is known about KRAS-mutant melanoma and further research is needed, but there is a possibility that one day KRAS will be a predictive biomarker for the development of early brain metastasis.

By understanding the genes involved in the development of early brain metastases, in the future, we may be able to provide a more accurate prognosis for patients, and be able to closely monitor them and intervene with treatment at an earlier stage, ultimately saving lives.

Publication:

Rabbie, R., Ferguson, P., Wong, K. et al. The mutational landscape of melanoma brain metastases presenting as the first visceral site of recurrence. Br J Cancer (2020).