BRAF-V600E mutation and its clinical significance in children with Langerhans cell histiocytosis
TANG Xue1, GUO Xia1, SUN Lin-Yong2, AI Yuan1, YANG Xue1, SUN Jing-Jing1, WU Jian-Rong1, GAO Ju1
Department of Pediatrics, West China Second University Hospital, Sichuan University/Key Laboratory of Birth Defects and Related Diseases of Women and Children
Abstract：Objective To investigate the clinical significance of BRAF-V600E mutation in children with Langerhans cell histiocytosis (LCH). Methods Real-time fluorescence quantitative PCR was used to detect BRAF-V600E mutation in paraffin-embedded tissue samples from 26 children with LCH. A retrospective analysis was performed for the association of BRAF-V600E mutation with clinical features and prognosis of children with LCH. Results Of the 26 children, 25 received standard chemotherapy, with a 2-year overall survival (OS) rate of 100% and a 2-year event-free survival (EFS) rate of 88%. Of the 26 pathological samples, 18 (70%) came from bone tissue, and the positive rate of BRAF-V600E mutation reached 50% (13/26). The positive rate of BRAF-V600E gene mutation was not associated with age, sex, affected organ, clinical classification, early treatment response, recurrence, and 2-year OS and EFS rates of the children with LCH (P > 0.05), but it was associated with clinical grouping of LCH (P < 0.05). Conclusions Children with LCH tend to have a high OS rate and a high incidence rate of BRAF-V600E mutation. BRAF-V600E mutation is associated with clinical grouping of LCH.
TANG Xue,GUO Xia,SUN Lin-Yong et al. BRAF-V600E mutation and its clinical significance in children with Langerhans cell histiocytosis[J]. CJCP, 2018, 20(4): 290-294.
Guyot-Goubin A, Donadieu J, Barkaoui M, et al. Descriptive epidemiology of childhood Langerhans cell histiocytosis in France, 2000-2004[J]. Pediatr Blood Cancer, 2008, 51(1):71-75.
[2]
Badalian-Very G, Vergilio JA, Fleming M, et al. Pathogenesis of Langerhans cell histiocytosis[J]. Annu Rev Pathol, 2013, 8:1-20.
[3]
Badalian-Very G, Vergilio JA, Degar BA, et al. Recurrent BRAF mutations in Langerhans cell histiocytosis[J]. Blood, 2010, 116(11):1919-1923.
[4]
Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer[J]. Nature, 2002, 417(6892):949-954.
Gadner H, Minkov M, Grois N, et al. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis[J]. Blood, 2013, 121(25):5006-5014.
[7]
Brown NA, Furtado LV, Betz BL, et al. High prevalence of somatic MAP2K1 mutations in BRAF V600E-negative Langerhans cell histiocytosis[J]. Blood, 2014, 124(10):1655-1658.
[8]
Chakraborty R, Hampton OA, Shen X, et al. Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis[J]. Blood, 2014, 124(19):3007-3015.
[9]
Nelson DS, Quispel W, Badalian-Very G, et al. Somatic activating ARAF mutations in Langerhans cell histiocytosis[J]. Blood, 2014, 123(20):3152-3155.
Sahm F, Capper D, Preusser M, et al. BRAF-V600E mutant protein is expressed in cells of variable maturation in Langerhans cell histiocytosis[J]. Blood, 2012, 120(12):e28-e34.
[12]
Héritier SS, Emile JF, Barkaoui MA, et al. BRAF mutation correlates with high-risk Langerhans cell histiocytosis and increased resistance to first-line therapy[J]. J Clin Oncol, 2016, 34(25):3023-3030.
[13]
Berres ML, Lim KP, Peters T, et al. BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups[J]. J Exp Med, 2014, 211(4):669-683.
[14]
Haroche J, Cohen-Aubart F, Emile JF, et al. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation[J]. Blood, 2013, 121(9):1495-1500.
[15]
Heritier S, Hélias-Rodzewicz Z, Lapillonne H, et al. Circulating cell-free BRAF-V600E as a biomarker in children with Langerhans cell histiocytosis[J]. Br J Haematol, 2017, 178(3):457-467.
