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A novel fusion gene PLEKHA6‐NTRK3 in langerhans cell histiocytosis
Author(s) -
Cai Jiaoyang,
Huang Xia,
Yin Minzhi,
Pan Ci,
Song Lili,
Zhan Zhiyan,
Chen Jing,
Gao Yijin,
Tang Jingyan,
Li Yanxin,
Shen Shuhong
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31636
Subject(s) - sanger sequencing , langerhans cell histiocytosis , mutation , biology , chromosomal translocation , fusion gene , cancer research , mapk/erk pathway , mutant , gene , genetics , signal transduction , medicine , pathology , disease
Langerhans cell histiocytosis (LCH) is the most common histiocytosis with constitutive activation of the RAS–RAF–MEK–ERK (MAPKinase) cell signaling pathway. We analyzed 89 cases of BRAF and MAP2K1 mutations by Sanger sequencing, of which 18 cases showed that these two gene mutations are negative. Whole genome sequencing of suitable specimens in these negative cases revealed a translocation from the 3 intron of PLEKHA6 to the 13 intron of NTRK3 in one case. We identified that this translocation could cause a novel fusion mutation, PLEKHA6‐NTRK3. Overexpression of the PLEKHA6‐NTRK3 mutant in NIH 3T3 cells enhanced MAPKinase pathway activation, promote cell growth. Our result suggested that a new mutation need be included in LCH molecular screening panel to better define its prevalence in LCH.