MedicalResearch: What is the background for this study?
Dr. Thomas: BRAF and NRAS mutations found in melanomas are important for tumor initiation and maintenance. There are drugs that target BRAF mutations or the pathway that are approved for BRAF-mutant metastatic melanoma and help improve survival. However, it remains unknown whether these mutations in primary melanoma are markers for melanomas with a worse prognosis.
MedicalResearch: What are the main findings?
- In a large international population-based study, we found that of primary melanomas, 30% harbor BRAF mutations, 13% have NRAS mutations and the other 57% do not have these mutations (wildtype).
- In higher primary tumor stage melanomas, BRAF or NRAS mutations were associated with an approximately 3-fold increased rate of death from melanoma compared to wildtype melanoma adjusted for other prognostic factors.
- Primary melanomas with NRAS mutations were less likely to have tumor infiltrating lymphocytes (TILs) in the tumor microenvironment.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Thomas: BRAF and NRAS mutations could be associated with worse survival in higher stage primary melanomas but this result needs to be replicated. NRAS mutant melanomas have fewer tumor infiltrating lymphocytes than the other molecular subtypes. This may affect how patients respond to immunotherapies.
Dr. Thomas: What recommendations do you have for future research as a result of this study?
Dr. Thomas: Further investigation as to whether BRAF or NRAS mutations in higher primary tumor stages are associated with worse survival.
Determining whether patients with NRAS-mutant melanoma respond as well to immunotherapies compared to those with BRAF-mutant or wildtype melanomas.
MedicalResearch.com Interview with: Nancy E. Thomas, MD, PhD (2015). Melanoma: BRAF or NRAS Mutations Associated With Worse Survival