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A novel fusion gene PLEKHA6‐NTRK3 in langerhans cell histiocytosis

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. Wh...

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Autores principales: Cai, Jiaoyang, Huang, Xia, Yin, Minzhi, Pan, Ci, Song, Lili, Zhan, Zhiyan, Chen, Jing, Gao, Yijin, Tang, Jingyan, Li, Yanxin, Shen, Shuhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587734/
https://www.ncbi.nlm.nih.gov/pubmed/30098202
http://dx.doi.org/10.1002/ijc.31636
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author Cai, Jiaoyang
Huang, Xia
Yin, Minzhi
Pan, Ci
Song, Lili
Zhan, Zhiyan
Chen, Jing
Gao, Yijin
Tang, Jingyan
Li, Yanxin
Shen, Shuhong
author_facet Cai, Jiaoyang
Huang, Xia
Yin, Minzhi
Pan, Ci
Song, Lili
Zhan, Zhiyan
Chen, Jing
Gao, Yijin
Tang, Jingyan
Li, Yanxin
Shen, Shuhong
author_sort Cai, Jiaoyang
collection PubMed
description 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.
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spelling pubmed-65877342019-07-02 A novel fusion gene PLEKHA6‐NTRK3 in langerhans cell histiocytosis Cai, Jiaoyang Huang, Xia Yin, Minzhi Pan, Ci Song, Lili Zhan, Zhiyan Chen, Jing Gao, Yijin Tang, Jingyan Li, Yanxin Shen, Shuhong Int J Cancer Molecular Cancer Biology 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. John Wiley & Sons, Inc. 2018-10-26 2019-01-01 /pmc/articles/PMC6587734/ /pubmed/30098202 http://dx.doi.org/10.1002/ijc.31636 Text en © 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Molecular Cancer Biology
Cai, Jiaoyang
Huang, Xia
Yin, Minzhi
Pan, Ci
Song, Lili
Zhan, Zhiyan
Chen, Jing
Gao, Yijin
Tang, Jingyan
Li, Yanxin
Shen, Shuhong
A novel fusion gene PLEKHA6‐NTRK3 in langerhans cell histiocytosis
title A novel fusion gene PLEKHA6‐NTRK3 in langerhans cell histiocytosis
title_full A novel fusion gene PLEKHA6‐NTRK3 in langerhans cell histiocytosis
title_fullStr A novel fusion gene PLEKHA6‐NTRK3 in langerhans cell histiocytosis
title_full_unstemmed A novel fusion gene PLEKHA6‐NTRK3 in langerhans cell histiocytosis
title_short A novel fusion gene PLEKHA6‐NTRK3 in langerhans cell histiocytosis
title_sort novel fusion gene plekha6‐ntrk3 in langerhans cell histiocytosis
topic Molecular Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587734/
https://www.ncbi.nlm.nih.gov/pubmed/30098202
http://dx.doi.org/10.1002/ijc.31636
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