Tang Xue, Gao Ju, Guo Xia, Wan Zhi, Sun Jing-Jing
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China.
Cancer Med. 2024 Dec;13(24):e70532. doi: 10.1002/cam4.70532.
Langerhans cell histiocytosis (LCH) is the most prevalent histiocytic disorder in pediatric populations, with a highly heterogeneous clinical presentation. Currently, the correlation between clinical phenotypes and molecular alterations in childhood LCH, besides the BRAF mutation, has not been sufficiently studied.
This study presented data on 33 pediatric LCH patients treated at our center who exhibited various molecular alterations other than the BRAF mutation. Additionally, we comprehensively reviewed pediatric LCH cases with non-BRAF molecular alterations reported from January 2010 to August 2024.
A total of 309 pediatric LCH patients with molecular alterations beyond BRAF were enrolled in the study, among whom 33 were from our center. In these LCH cases, 49 kinds of MAP2K1 mutations, 31 kinds of BRAF mutations, and 4 kinds of ARAF mutations were found. At our center, two patients with multisystem LCH with risk organ involvement, both with BRAF mutation, showed poor response to induction chemotherapy for 6 weeks. Among the 303 LCH patients with MAP2K1 or other BRAF alterations, patients with the MAP2K1 mutation had a higher prevalence of single-system bone involvement (SS-bone) than patients carrying the BRAF mutation (p = 0.0072). Within the MAP2K1 group, exon 3 mutations exhibited a stronger association with SS-bone than exon 2 mutations (p = 0.042). Additionally, patients with the BRAF exon 15 mutation and MAP2K1 exon 2 mutation had higher rates of LCH onset before age 3 compared with patients carrying the BRAF exon 12 mutation and MAP2K1 exon 3 mutation (p = 0.037; p = 0.0015). Patients carrying the BRAF mutation in exon 15 had higher rates of liver involvement compared with patients carrying the exon 12 (p = 0.042).
Pediatric LCH patients often carry recurrent somatic MAP2K1 and BRAF mutations, which are associated with clinical manifestations.
朗格汉斯细胞组织细胞增多症（LCH）是儿科人群中最常见的组织细胞疾病，临床表现高度异质性。目前，除BRAF突变外，儿童LCH临床表型与分子改变之间的相关性尚未得到充分研究。
本研究展示了在我们中心接受治疗的33例儿科LCH患者的数据，这些患者表现出除BRAF突变外的各种分子改变。此外，我们全面回顾了2010年1月至2024年8月报告的具有非BRAF分子改变的儿科LCH病例。
共有309例具有BRAF以外分子改变的儿科LCH患者纳入研究，其中33例来自我们中心。在这些LCH病例中，发现了49种MAP2K1突变、31种BRAF突变和4种ARAF突变。在我们中心，两名有多系统LCH且有风险器官受累的患者均有BRAF突变，对诱导化疗6周反应不佳。在303例有MAP2K1或其他BRAF改变的LCH患者中，MAP2K1突变患者单系统骨受累（SS-骨）的患病率高于携带BRAF突变的患者（p = 0.0072）。在MAP2K1组中，外显子3突变与SS-骨的关联比外显子2突变更强（p = 0.042）。此外，与携带BRAF外显子12突变和MAP2K1外显子3突变的患者相比，携带BRAF外显子15突变和MAP2K1外显子2突变的患者LCH发病年龄在3岁之前的比例更高（p = 0.037；p = 0.0015）。与携带外显子12的患者相比，携带外显子15 BRAF突变的患者肝脏受累比例更高（p = 0.042）。
儿科LCH患者常携带复发性体细胞MAP2K1和BRAF突变，这些突变与临床表现相关。
