Michael Krauthammer, MD, PhD, Associate Professor of Pathology, Yale School of Medicine, discusses the role of NF1 mutation in melanoma.

A recent analysis, conducted by Krauthammer and his team at Yale, established NF1, which encodes a negative regulator of RAS, as the third most frequently mutated gene in melanoma, after BRAF and NRAS.

While BRAF makes up approximately 50% of all melanomas,and NRAS makes up 20%, it was previously unknown what made up the remaining 30% of melanomas. It has now been determined the NF1 mutations account for 12% of melanomas, providing another piece of the puzzle in fully understanding all melanoma mutations, says Krauthammer.

Because NF1 activates the same pathways as BRAF and NRAS, MEK inhibition should work well in patients who have the mutation, says Krauthammer. Several studies are currently investigating MEK inhibitors in NF1-mutated melanoma including the nationwide GEMM trial and the NCI Match trial, says Krauthammer. Oncologists who have patients with BRAF wild type melanoma who have failed other therapies should consider enrolling them into one of these trials, says Krauthammer.

Michael Krauthammer, MD, PhD

Articles

Dr. Michael Krauthammer on NF1 Mutations in Melanoma