Studying mutational changes during melanoma progression.

When a melanoma appears for the first time it is usually localized, removed by surgery, and presents little risk for the patient. But danger arises when this tumour decides to travel and deposit somewhere else in the body – a process called metastasis. While genetic mutations in cells that cause melanomas to appear have been well characterized, the mutations that occur with metastasis to distant organs such as the liver, lungs and brain are less well understood. A major reason for this is the difficulty in accessing tumours from distant organs. As a result, a pioneering program was implemented at Peter Mac to allow acquisition of such tissue samples with the consent of patients and families. This provides opportunity to investigate key mutations that drive metastasis.

We have performed this analysis on tumors from seven patients so far. We have found that each patient represents a unique world of genetic mutations that develop during metastasis. Despite this, we find common patterns across the cases. Unexpectedly, very small new mutations called ‘SNVs’ usually develop only minimally during metastasis. In contrast, mutations that either eliminate or add large chunks of DNA to chromosomes in the cells increase dramatically. This suggests that such large mutations efficiently provide melanoma cells with important properties that help them spread and grow in patients. The next phase of our work will be to find out how these large mutations occur, and how melanoma cells survive and thrive in spite and as a result of them.