Recurrent BRAF mutations in Langerhans cell histiocytosis
Recurrent BRAF mutations in Langerhans cell histiocytosis
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DOI：
10.1182/blood-2010-04-279083
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发表时间：
2010-09-16
期刊：
影响因子：
20.3
通讯作者：
Rollins, Barrett J.
中科院分区：
文献类型：
--
作者：
Badalian-Very, Gayane;Vergilio, Jo-Anne;Rollins, Barrett J.
朗格汉斯细胞组织细胞增生症（LCH）具有广泛的临床行为谱；一些病例为自限性，而其他病例累及多个器官并导致显著的死亡率。尽管LCH中的朗格汉斯细胞是克隆性的，但它们良性的形态以及（到目前为止）缺乏报道的反复出现的基因组异常，表明LCH可能不是肿瘤。在此，我们使用两种正交技术检测福尔马林固定、石蜡包埋材料中与癌症相关的突变，在61份存档标本中的35份（57%）中鉴定出致癌的BRAF V600E突变。在各一份样本中还观察到TP53和MET突变。BRAF V600E倾向于出现在较年轻的患者中，但与疾病部位或分期无关。无论突变状态如何，朗格汉斯细胞都对磷酸化丝裂原活化蛋白激酶激酶（磷酸化 - MEK）和磷酸化细胞外信号调节激酶（磷酸化 - ERK）染色。LCH中BRAF突变的高患病率和复发性表明它是一种可能对RAF通路抑制剂有反应的肿瘤性疾病。（《血液》2010年；116(11): 1919 - 1923）
Langerhans cell histiocytosis (LCH) has a broad spectrum of clinical behaviors; some cases are self-limited, whereas others involve multiple organs and cause significant mortality. Although Langerhans cells in LCH are clonal, their benign morphology and their lack (to date) of reported recurrent genomic abnormalities have suggested that LCH may not be a neoplasm. Here, using 2 orthogonal technologies for detecting cancer-associated mutations in formalin-fixed, paraffin-embedded material, we identified the oncogenic BRAF V600E mutation in 35 of 61 archived specimens (57%). TP53 and MET mutations were also observed in one sample each. BRAF V600E tended to appear in younger patients but was not associated with disease site or stage. Langerhans cells stained for phosphomitogen-activated protein kinase kinase (phospho-MEK) and phospho-extracellular signal-regulated kinase (phospho-ERK) regardless of mutation status. High prevalence, recurrent BRAF mutations in LCH indicate that it is a neoplastic disease that may respond to RAF pathway inhibitors. (Blood. 2010; 116(11): 1919-1923)