Analysis of the BRAF and MAP2K1 mutations in patients with Langerhans cell histiocytosis in Japan
- PDF / 836,366 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 20 Downloads / 217 Views
ORIGINAL ARTICLE
Analysis of the BRAF and MAP2K1 mutations in patients with Langerhans cell histiocytosis in Japan Tomomi Hayase1 · Shiori Saito1 · Yoko Shioda2 · Toshihiko Imamura3 · Kenichiro Watanabe4 · Kentaro Ohki5 · Takako Yoshioka6 · Yukiko Oh1 · Yuta Kawahara1 · Hitomi Niijima1 · Shinsaku Imashuku7 · Akira Morimoto1 Received: 13 February 2020 / Revised: 11 June 2020 / Accepted: 23 June 2020 © Japanese Society of Hematology 2020
Abstract In Langerhans cell histiocytosis (LCH), somatic gene mutations in the mitogen-activated protein kinase pathway have been identified in more than 80% of cases in Western countries, in which mutually exclusive BRAF and MAP2K1 mutations are involved. Among them, BRAF V600E mutation is the major contributor (50–60%). In 59 patients (50 children and nine adults) with LCH (not including pulmonary LCH) in Japan, we first screened for BRAF V600E in all patients followed by target sequencing for other gene mutations in 17 of BRAF V600E-negative patients. As a result, BRAF V600E mutation was detected in 27/59 (46%) patients. We also identified BRAF mutations other than V600E in five and MAP2K1 mutations in nine patients. Thus, gene mutations in BRAF or MAP2K1 were identified in 41/44 (93%) of the fully tested patients. Regarding the correlation of clinical features and genotype in pediatric patients, we found that BRAF V600E mutation status was not correlated with sex, age at diagnosis, disease extent, response to first-line therapy, relapse, or CNS-related sequelae. Interestingly, MAP2K1 exon 2 in-frame deletion was related to the risk organ involvement; however, further studies are required to clarify the impact of these gene mutations on the clinical features of patients with LCH. Keywords Langerhans cell histiocytosis · BRAF V600E mutation · MAP2K1 mutation · Clinical outcome
Introduction
* Akira Morimoto [email protected] 1
Department of Pediatrics, Jichi Medical University, 3311‑1 Yakushiji, Shimotsuke, Tochigi 329‑0498, Japan
2
Department of Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan
3
Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan
4
Department of Hematology and Oncology, Shizuoka Children’s Hospital, Shizuoka, Japan
5
Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan
6
Department of Pathology, National Center for Child Health and Development, Tokyo, Japan
7
Division of Laboratory Medicine, Uji Tokushukai Medical Center, Uji, Japan
Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by the accumulation of CD1a+CD207+ immature dendritic cells and infiltration of inflammatory cells in the lesion. Patients with LCH present with a wide spectrum of clinical manifestations, from a solitary lesion that regresses spontaneously without treatment, to multi-system lesions, which are sometimes chemotherapy-resistant and can lead to death [1]. In 2010, BRAF V600E
Data Loading...
