Malignant Melanoma with Concurrent BRAF E586K and NRAS Q81K Mutations

Abstract

Cutaneous melanoma is an aggressive malignant tumor of melanocytes which accounts for 80% of skin cancer-related deaths. A number of driver mutations have been identified in melanoma, with the mutually exclusive BRAF V600E and NRAS Q61A mutations together accounting for roughly 70% of mutations. Simultaneous BRAF V600E and NRAS Q61A mutations in melanoma are rare, with evidence suggesting that up to 2.9% (2/69) of primary cutaneous melanomas carry both mutations. Here we describe a 42-year-old man with concurrent BRAF E586K and NRAS Q81K driver mutations. To our knowledge, this is the first description of these driver mutations occurring simultaneously in primary cutaneous melanoma.

Spatially Resolved Genetic Analysis of Tissue Sections Enabled by Microscale Flow Confinement Retrieval and Isotachophoretic Purification

“…The BRAF E586K mutation is less common than the V600E but is also known to be associated with melanoma. [13] We note that despite the high purification yield, we did not observe amplification in all footprints from RKO samples.T his may be due to the lower cell density when compared to the MCF-7 cells,dilution of replicates for PCR, and impurities remnant in the ITP sample,which may impede the PCR reaction.…”

“…The Sanger sequencing result for MCF‐7 sample B2 (wildtype, Figure e) and sample B3 (mutated, Figure f) show an accurately resolved G>A substitution on position 1756, also known as E586K. The BRAF E586K mutation is less common than the V600E but is also known to be associated with melanoma . We note that despite the high purification yield, we did not observe amplification in all footprints from RKO samples.…”

Beyond the BRAF V 600E hotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients

“…Shackelford et al . described the case of a 42‐year‐old male patient with a BRAF E586K and a NRAS Q61 mutation . Unfortunately, no therapeutic interventions were described in this case report, but the authors concluded from their case that, due to the BRAF/NRAS double mutation, a BRAF inhibitor would have been counterproductive.…”