Your browser doesn't support javascript.
loading
Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis.
Wang, Chan-Juan; Cui, Lei; Li, Shuang-Shuang; Ma, Hong-Hao; Wang, Dong; Lian, Hong-Yun; Zhao, Yun-Ze; Zhang, Li-Ping; Li, Wei-Jing; Zhang, Qing; Zhao, Xiao-Xi; Yang, Ying; Huang, Xiao-Tong; Liu, Wei; Wang, Yi-Zhuo; Wu, Wan-Shui; Wang, Tian-You; Zhang, Rui; Li, Zhi-Gang.
Afiliação
  • Wang CJ; From the Laboratory of Hematologic Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China; (C-J Wang, Cui, W-J Li, Q Zhang, X-X Zhao, Huang, Z-G Li).
  • Cui L; From the Laboratory of Hematologic Diseases, Beijing Key Laboratory of Pediatric Hematology Oncology, Hematology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zha
  • Li SS; National Key Discipline of Pediatrics, Capital Medical University, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zhang, X-X Zhao, Yang, Huang, T-Y Wang, R Zhang, Z-G Li).
  • Ma HH; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zhang, X-X Zhao, Yang, Huang, T-Y Wang, R Zhang, Z-G Li).
  • Wang D; From the Laboratory of Hematologic Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China; (C-J Wang, Cui, W-J Li, Q Zhang, X-X Zhao, Huang, Z-G Li).
  • Lian HY; From the Laboratory of Hematologic Diseases, Beijing Key Laboratory of Pediatric Hematology Oncology, Hematology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zha
  • Zhao YZ; National Key Discipline of Pediatrics, Capital Medical University, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zhang, X-X Zhao, Yang, Huang, T-Y Wang, R Zhang, Z-G Li).
  • Zhang LP; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zhang, X-X Zhao, Yang, Huang, T-Y Wang, R Zhang, Z-G Li).
  • Li WJ; MyGenostics Inc, Beijing, China (S-S Li).
  • Zhang Q; From the Laboratory of Hematologic Diseases, Beijing Key Laboratory of Pediatric Hematology Oncology, Hematology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zha
  • Zhao XX; National Key Discipline of Pediatrics, Capital Medical University, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zhang, X-X Zhao, Yang, Huang, T-Y Wang, R Zhang, Z-G Li).
  • Yang Y; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zhang, X-X Zhao, Yang, Huang, T-Y Wang, R Zhang, Z-G Li).
  • Huang XT; From the Laboratory of Hematologic Diseases, Beijing Key Laboratory of Pediatric Hematology Oncology, Hematology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zha
  • Liu W; National Key Discipline of Pediatrics, Capital Medical University, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zhang, X-X Zhao, Yang, Huang, T-Y Wang, R Zhang, Z-G Li).
  • Wang YZ; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zhang, X-X Zhao, Yang, Huang, T-Y Wang, R Zhang, Z-G Li).
  • Wu WS; From the Laboratory of Hematologic Diseases, Beijing Key Laboratory of Pediatric Hematology Oncology, Hematology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zha
  • Wang TY; National Key Discipline of Pediatrics, Capital Medical University, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zhang, X-X Zhao, Yang, Huang, T-Y Wang, R Zhang, Z-G Li).
  • Zhang R; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zhang, X-X Zhao, Yang, Huang, T-Y Wang, R Zhang, Z-G Li).
  • Li ZG; From the Laboratory of Hematologic Diseases, Beijing Key Laboratory of Pediatric Hematology Oncology, Hematology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China (C-J Wang, Cui, Ma, D Wang, Lian, Y-Z Zhao, L-P Zhang, W-J Li, Q Zha
Arch Pathol Lab Med ; 2024 May 16.
Article em En | MEDLINE | ID: mdl-38749502
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.
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article