Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis

作者：Chanjuan Wang, Lei Cui, Shuangshuang Li, Honghao Ma, Dong Wang, Hongyun Lian, Yunze Zhao, Li-Ping Zhang, Weijing Li, Qing Zhang, Xiaoxi Zhao, Ying Yang, Xiao‐Tong Huang, Wei Liu, Yi-Zhuo Wang, Wanshui Wu, Tianyou Wang, Rui Zhang, Zhigang Li · 发表于：Archives of Pathology & Laboratory Medicine · 年份：2024 · DOI：10.5858/arpa.2023-0236-oa · 被引用次数：9 · 研究领域：Histiocytic Disorders and Treatments、Skin Diseases and Diabetes、Genetic and rare skin diseases.

CONTEXT.—: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm that predominantly affects young children. OBJECTIVE.—: To investigate genetic alterations and their correlation with clinical characteristics and prognosis in pediatric LCH. DESIGN.—: We performed targeted sequencing to detect mutations in LCH lesions from pediatric patients. RESULTS.—: A total of 30 genomic alterations in 5 genes of the MAPK pathway were identified in 187 of 223 patients (83.9%). BRAF V600E (B-Raf proto-oncogene, serine/threonine kinase) was the most common mutation (51.6%), followed by MAP2K1 (mitogen-activated protein kinase kinase 1) alterations (17.0%) and other BRAF mutations (13.0%). ARAF (A-Raf proto-oncogene, serine/threonine kinase) and KRAS (KRAS proto-oncogene, GTPase) mutations were relatively rare (2.2% and 0.9%, respectively). Additionally, FNBP1 (formin-binding protein 1)::BRAF fusion and MAP3K10 (mitogen-activated protein kinase kinase 10) mutations A17T and R823C were identified in 1 case each, with possible constitutive activation of ERK1/2 phosphorylation. BRAF V600E was more frequent in patients with risk organ involvement, while MAP2K1 mutation was more prevalent in patients with single-system LCH (P = .001). BRAF V600E was associated with craniofacial bone, skin, liver, spleen, and ear involvement (all P < .05). Patients with other BRAF mutations had a higher proportion of spinal column involvement (P = .006). Univariate analysis showed a significant difference i...