A novel fusion gene PLEKHA6-NTRK3 in langerhans cell histiocytosis.
A novel fusion gene PLEKHA6-NTRK3 in langerhans cell histiocytosis.
复制标题
朗格汉斯细胞组织细胞增生症中的新型融合基因 PLEKHA6-NTRK3
DOI：
10.1002/ijc.31636
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发表时间：
2019-01-01
影响因子：
6.4
通讯作者：
Shen S
中科院分区：
文献类型：
--
作者：
Cai J;Huang X;Yin M;Pan C;Song L;Zhan Z;Chen J;Gao Y;Tang J;Li Y;Shen S
朗格汉斯细胞组织细胞增生症（LCH）是最常见的组织细胞增生症，具有RAS-RAF-MEK-ERK（MAP激酶）细胞信号通路的组成性激活。我们通过桑格测序分析了89例BRAF和MAP 2K 1基因突变，其中18例显示这两个基因突变为阴性。对这些阴性病例中的合适标本进行全基因组测序，发现一例病例中PLEKHA 6的3个内含子易位至NTRK 3的13个内含子。我们发现这种易位可能导致一种新的融合突变PLEKHA 6-NTRK 3。PLEKHA 6-NTRK 3突变体在NIH 3 T3细胞中的过表达增强了MAP激酶通路的激活，促进细胞生长。我们的结果提示，LCH分子筛查中需要包括一个新的突变，以更好地确定其在LCH中的患病率。 有什么新消息吗？ 朗格汉斯细胞组织细胞增生症（LCH）是一种罕见的免疫和肿瘤性疾病。虽然它被认为是最常见的组织细胞增生症，伴有RAS-RAF-MEK-ERK（MAP激酶）细胞信号通路的组成性激活，但其发病机制仍不清楚。在这里，BRAF V600 E阴性和MAP 2K 1阴性LCH病例的全基因组测序显示，在一名患者中，PLEKHA 6的内含子3易位到NTRK 3的内含子13，鉴定出一种新的融合突变。体外过表达PLEKHA 6-NTRK 3增强MAP激酶通路活化，促进细胞生长。结果支持将融合突变纳入LCH分子筛查组，以更好地确定其在患者中的患病率。
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. What's new? Langerhans cell histiocytosis (LCH) is a rare immune and neoplastic disorder. While it is known as the most common histiocytosis with constitutive activation of the RAS‐RAF‐MEK‐ERK (MAPKinase) cell signaling pathway, its pathogenesis remains obscure. Here, whole‐genome sequencing of BRAF V600E‐negative and MAP2K1‐negative LCH cases revealed a translocation from the intron 3 of PLEKHA6 to the intron 13 of NTRK3 in one patient, identifying a novel fusion mutation. Overexpression of PLEKHA6‐NTRK3 in vitro enhanced MAPKinase pathway activation, promoting cell growth. The results support the inclusion of the fusion mutation in LCH molecular screening panel to better define its prevalence in patients.
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影响因子：
28.2
作者：
Diamond EL;Durham BH;Haroche J;Yao Z;Ma J;Parikh SA;Wang Z;Choi J;Kim E;Cohen-Aubart F;Lee SC;Gao Y;Micol JB;Campbell P;Walsh MP;Sylvester B;Dolgalev I;Aminova O;Heguy A;Zappile P;Nakitandwe J;Ganzel C;Dalton JD;Ellison DW;Estrada-Veras J;Lacouture M;Gahl WA;Stephens PJ;Miller VA;Ross JS;Ali SM;Briggs SR;Fasan O;Block J;Héritier S;Donadieu J;Solit DB;Hyman DM;Baselga J;Janku F;Taylor BS;Park CY;Amoura Z;Dogan A;Emile JF;Rosen N;Gruber TA;Abdel-Wahab O
通讯作者：
Abdel-Wahab O
影响因子：
20.3
作者：
Badalian-Very, Gayane;Vergilio, Jo-Anne;Rollins, Barrett J.
通讯作者：
Rollins, Barrett J.
影响因子：
51.1
作者：
Grob, Jean Jacques;Amonkar, Mayur M.;Robert, Caroline
通讯作者：
Robert, Caroline
影响因子：
20.3
作者：
Chakraborty, Rikhia;Hampton, Oliver A.;Parsons, D. Williams
通讯作者：
Parsons, D. Williams
影响因子：
30.8
作者：
Knezevich, SR;McFadden, DE;Sorensen, PHB
通讯作者：
Sorensen, PHB