Affiliations: [a] Clinical Oncology Research Institute, N. N. Blokhin Russian Cancer Research Center of Russian Academy of Medical Sciences, Moscow, Russia | [b] Engelhardt Institute of Molecular Biology of Russian Academy of Sciences, Moscow, Russia | [c] Institute of Molecular Biology and Biophysics, Novosibirsk, Russia
Correspondence:
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Corresponding author: Tatyana Nasedkina, Laboratory for Biological Microchips, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Russian Federation, Moscow, Vavilova str., 32, Russia. Tel.: +7 9169092440; Fax: +7 4991351405; E-mail:[email protected]
Abstract: BACKGROUND: The activating mutation BRAF V600E is considered to be a
diagnostic cutaneous melanoma (CM) marker important for prognosis and
targeted therapy. OBJECTIVE: The aim of this study was to determine the
frequency of the V600E mutation in CM patients in Russia and to estimate the
influence of the BRAF gene mutation status on prognosis and clinical outcome. METHODS: To ensure mutation detection in FFPE tissue,
interlaboratory validation was performed using three different methods:
allele-specific hybridisation on a biochip, allele-specific real-time PCR
and, in some cases, direct sequencing. RESULTS: Mutation V600E was detected in 49% of
patients. The age of disease manifestation was significantly lower in
mutated (MT) BRAF patients, and the median age difference between the wild-type
(WT) and MT BRAF groups (P= 0.002) was 10 years. A tumour thickness more than 1 mm
was also more frequently observed in the MT BRAF group (P= 0.059). Patients from
the MT BRAF group were more likely to have ulceration compared to the WT group
(P= 0.088). No statistically significant differences were found between the
relapse-free, progression-free or overall survival of CM patients in the MT
BRAF and WT BRAF groups. CONCLUSIONS: The data obtained show that the V600E BRAF mutation
occurred in about half of melanoma patients; it was associated with earlier
manifestation of melanoma and likely with more aggressive clinical features.
