engleski

BRAF V600E and V600K mutations in Croatian patients with melanoma

BRAF mutations, which are found in 40–60% of all melanomas, are predictive marker for targeted therapy with BRAF-inhibitors in patients with metastatic melanoma. 80–90% of all BRAF mutations in melanoma are V600E and next in frequency (10-20%) is V600K. The aim of this study was to determine the frequency of V600E and V600K BRAF mutations and association between gender, age and type of sample material (primary melanoma or metastasis) with presence and type of BRAF mutation in melanomas from patients treated at University Hospital Sestre milosrdnice, Croatia. To our knowledge this will be the first such study for Croatian population. DNA was isolated from archived formalin-fixed paraffin-embedded (FFPE) melanoma tissue and assayed by real-time PCR for BRAF V600E and BRAF V600K mutations using specific TaqMan probes. For statistical analysis Mann-Whitney U test or χ2 test were used, depending on type of variable. A total of 189 samples (57 primary melanomas, 132 metastases) from 177 patients (97 male, 80 female ; age 21-89 years, median 62 years) were analysed. Among 189 samples, 54% had BRAF mutation (11% V600K and 43% V600E), 41% did not have BRAF mutation, and 9 (5%) were inadequate for the analysis. In 8 patients two different lesions (primary melanoma and metastasis or 2 different metastases) were analysed and in one of these patients results were discordant, primary melanoma had V600E mutation and metastasis did not have BRAF mutations. Patients with BRAF mutations were significantly younger than patients without BRAF mutation (median age 59 and 67 years, p=0, 0005). Among patients with BRAF mutation, ones with V600E mutation were significantly younger than ones with V600K mutation (median age 56 and 71 years, p=0, 0001). Frequency of BRAF mutations was significantly higher in male patients than in female patients (p=0, 001). Frequency of BRAF mutations was significantly higher in samples from metastases than in samples from primary melanoma (p=0, 032). Frequency of BRAF V600E and V600K mutations and association with age shown in our patients is concordant with previously published results in other populations of melanoma patients. Discrepancy in BRAF mutation status between primary melanoma and metastasis shown in one patient warrants that inter-lesional heterogeneity should be taken into account while interpreting BRAF mutation analysis results.

melanoma; BRAF; mutations; V600E; V600K

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