Frequent BRAFV600E mutation has no effect on tumor invasiveness in patients with Langerhans cell histiocytosis

The oncogenic BRAFV600E mutation in patients with Langerhans cell histiocytosis (LCH) has recently been reported. However, the reported frequencies were significantly inconsistent and were based on studies of populations of western ethnic origin. The aim of this study was to identify the presence of BRAFV600E mutation in a cohort of Chinese LCH patients and to determine its association with clinicopathological characteristics. Blocks were retrieved from 52 LCH patients and 12 samples were obtained from blood or bone marrow. These were tested for BRAFV600E by directly sequencing the entire exon 15 of the BRAF gene. To demonstrate the relationship between BRAFV600E and invasiveness of LCH, the single or multiple systems classification was used. BRAFV600E was the only genetic abnormality within exon 15 of the BRAF gene in patients with LCH. Its incidence was 56%, similar to that reported in a United States study, but higher than that reported in German studies. Additionally, the frequencies were similar between patients with single system diseases and those with multiple system diseases. Results of this study showed that BRAFV600E was present in a large number of the Chinese LCH patients, confirming the neoplastic nature of LCH. The frequency was similar to that of the USA study but distinctly higher than that from the Europe studies. No additional mutation were identified besides BRAFV600E. This mutation did not closely correlate with clinical severity or classification. The finding of BRAFV600E in LCH has important implications for both molecular diagnosis and targeted personalized therapy.