Association between development of Langerhans cell histiocytosis and polymorphism in the Toll-like receptor pathways

Research Project

Project/Area Number	24791084
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Pediatrics
Research Institution	Jichi Medical University
Principal Investigator	Hayase Tomomi 自治医科大学, 医学部, 助教 (50433587)
Project Period (FY)	2012-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	ランゲルハンス細胞組織球症 / トル様受容体 / BRAF / MAP2K1 / 全エクソンシークエンス解析 / リアルタイムPCR / Toll様受容体 / MEK1 / 全エクソン解析 / アンプリコン解析 / エクソーム解析 / ランゲルハンス細胞組織旧称
Outline of Final Research Achievements	Langerhans cell histiocytosis (LCH) is characterized by proliferation of immature dendritic cells and infiltration of inflammatory cells. We analyzed expression of toll-like receptors (TLRs) in LCH cells and found that TLR1, 2, 6, 7, 8 was over expressed. Whole exome sequencing (WES) was performed on paired samples of LCH lesions and normal tissues obtained form 5 patients. Mutation specific PCR for BRAF was performed in 16 LCH samples. No mutation of TLRs was found but previously reported MAP2K1 mutation was found in 3 of 5 patients by WES. BRAFV600E mutation was found in 6 of 16 LCH samples by PCR.