BRAF Mutations Are More Frequent in Younger Patients and Are Inversely Associated with Degree of Dysplasia in Melanocytic Neoplasms
Cary Chisholm, Daniel Smith, Kimberly Walker, John F Greene, Arundhati Rao. Scott & White Memorial Hospital, Temple, TX
Background: Mutations in the BRAF gene, particularly the V600E mutation, have been postulated to be early somatic events occurring in common nevi, but data regarding the association have been limited and contradictory. While specific therapeutic inhibitors of BRAF V600E mutants have been developed and have shown great promise in the treatment of metastatic melanoma, the mutation status has not been correlated with the degree of dysplasia, age, gender, or frequency of the mutation in dysplastic nevi.
Design: We identified 129 dysplastic nevi: 43 with mild dysplasia, 44 with moderate dysplasia, and 42 with severe dysplasia. 11 benign compound nevi and 10 melanoma specimens were also examined. Once retrieved from storage, the lesions underwent laser-capture micro-dissection and subsequent semi-quantitative testing for BRAF V600E gene mutations.
Results: The frequency of BRAF mutations and percent of heterozygosity was inversely proportional to the degree of dysplasia (p<0.04) (see table). 5/7 patients with personal or familial history of melanoma and multiple dysplastic nevi had BRAF V600E mutations. Patients with BRAF mutations were younger than wild type (median 43 years versus 54 years, p<0.0001). Women with BRAF mutations were younger than their male counterparts in each group.
|Compound Nevi (n=11)||Mildly Dysplastic Nevi (n=43)||Moderately Dysplastic Nevi (n=44)||Severely Dysplastic Nevi (n=42)||Melanoma (n=10)|
|Mean Age (years)|
|Wild type (WT)||41.25||50.25||52.8||52.8||81.1|
|Frequency of BRAF V600E mutations||64%||54%||46%||31%||30%|