AI Article Synopsis
- Langerhans cell histiocytosis (LCH) is a rare cancer mainly affecting young children, and this study aimed to understand its genetic changes and how they relate to clinical outcomes.
- Researchers identified 30 genetic mutations in 5 key genes of the MAPK pathway in 83.9% of the pediatric patients studied, with BRAF V600E being the most common mutation.
- The presence of specific mutations was linked to different clinical features and survival rates, indicating that mutations like BRAF V600E are associated with more severe cases involving vital organs.
Article Abstract
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 in progression-free survival among the 4 molecular subgroups for patients treated with first-line therapy (P = .02). According to multivariate analysis, risk organ involvement was the strongest independent adverse prognostic factor (hazard ratio, 8.854; P < .001); BRAF or MAP2K1 mutation was not an independent prognostic factor.
Conclusions.—: Most pediatric patients with LCH carry somatic mutations involving the MAPK pathway, correlating with clinical characteristics and outcomes for first-line chemotherapy.
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Source |
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| http://dx.doi.org/10.5858/arpa.2023-0236-OA | DOI Listing |
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