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

Abstract

Abstract. 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 BRAF V600E 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 BRAF V600E by directly sequencing the entire exon 15 of the BRAF gene. To demonstrate the relationship between BRAF V600E and invasiveness of LCH, the single or multiple systems classification was used. BRAF V600E 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 BRAF V600E 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 BRAF V600E . This mutation did not closely correlate with clinical severity or classification. The finding of BRAF V600E in LCH has important implications for both molecular diagnosis and targeted personalized therapy.

Association between clinicopathologic characteristics and BRAFV600E expression in Chinese patients with Langerhans cell histiocytosis

“…However, only four patients (6%) in our cohort were diagnosed with solitary PLCH. Most of the previous studies did not show the completed screening tests for the enrolled patients with LCH . In our study, all 67 patients underwent strict screening tests including chest CTs, cranial MRIs, bone scans and bone marrow biopsies, with the exception of detailed serum tests.…”

“…No BRAF V600E mutations were reported in adults with LCH in the study by Tong et al ., but in the studies by Wei et al . and Zeng et al ., the frequencies of BRAF V600E mutations were 17.3% and 15.6% for Chinese adult patients with LCH and 46.4% and 32% for all recruited patients with LCH, respectively. Here, we retrospectively analyzed BRAF V600E mutations and the clinical features of patients with LCH with a positive pathological diagnosis at our hospital over the last five years.…”

“…reported that younger LCH patients tended to be positive for BRAF V600E mutations, and most patients with BRAF V600E mutations in the study by Wei et al . had bone involvement or the MS‐LCH subtype; in the study by Tong et al . 3,4,8 skin and lung were the most commonly involved sites, and 77.8% of the patients had the LCH‐SS subtype.…”

The use of droplet digital polymerase chain reaction for the molecular diagnosis and monitoring of treatment response in patients with Langerhans cell histiocytosis with the <i>BRAF</i> V600E mutation

“…Во многих исследованиях было показано, что у 50-60% пациентов с ГКЛ обнаруживается точечная соматическая мутация BRAF V600E, приводящая к митотической активации и ингибированию апоптоза [3][4][5]. Ранее считалось, что распространенность поражения при гистиоцитозе зависит от уровня дифференцировки клеток, на котором происходит мутация и активация RAS/RAF-MEK-ERK-сигнального пути.…”

Clinicogenomic associations in patients with Langerhans cell histiocytosis: a cohort study

“…Множество исследований показали, что у 50-60% пациентов с ГКЛ обнаруживается точечная соматическая мутация BRAF V600E, приводящая к митотической активации и ингибированию апоптоза [2,3].…”