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Whole exome sequencing reveals novel somatic alterations in neuroblastoma patients with chemotherapy
BACKGROUND: We ought to explore the acquired somatic alterations, shedding light on genetic basis of somatic alterations in NB patients with chemotherapy. METHODS: Marrow blood samples from NB patients were collected before treatment, after the 2nd and 4th chemotherapy for baseline research and cont...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816515/ https://www.ncbi.nlm.nih.gov/pubmed/29467591 http://dx.doi.org/10.1186/s12935-018-0521-3 |
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author | Duan, Chao Wang, Han Chen, Ying Chu, Ping Xing, Tianyu Gao, Chao Yue, Zhixia Zheng, Jie Jin, Mei Gu, Weiyue Ma, Xiaoli |
author_facet | Duan, Chao Wang, Han Chen, Ying Chu, Ping Xing, Tianyu Gao, Chao Yue, Zhixia Zheng, Jie Jin, Mei Gu, Weiyue Ma, Xiaoli |
author_sort | Duan, Chao |
collection | PubMed |
description | BACKGROUND: We ought to explore the acquired somatic alterations, shedding light on genetic basis of somatic alterations in NB patients with chemotherapy. METHODS: Marrow blood samples from NB patients were collected before treatment, after the 2nd and 4th chemotherapy for baseline research and continuous monitoring by whole exome sequencing. Plasma cell free DNA (cfDNA) was prepared for baseline research. Finger nail cells were extracted as self control. The clinical data was analyzed. RESULTS: From December 2014 to February 2016, 27 cases of children with stage IV NB were diagnosed. The follow up time ranged from 5 to 25 months, with a median follow up time of 17 months, 20 patients were stable, one patient died of pulmonary embolism during surgery, six patients died of disease progression. Marrow blood whole exome sequencing demonstrated that several novel somatic mutations were identified in all three trios comply or against the trendy of tumor size variation. Of note, six recurrent mutations in bromodomain PHD finger transcription factor (BPTF) were identified in nine NB patients under the continuous monitoring. The mutation rates variation was positively correlated to tumor size (CC = 0.428, P = 0.021), and patients with BPTF mutation may have a worse prognosis compared with wild type. Meanwhile, CGREF1, CUX2, GP1BA, SLC45A1 and TRA2A were mutated with the trendy oppose as therapeutic effects. The baseline research in three NB patients demonstrated that mutation rate of BPTF, TMCO3, GPRIN2 and C20orf96 in plasma cfDNA were in positive correlation with bone marrow genomic DNA (P = 0.001). CONCLUSIONS: Our study showed that BPTF along with other mutations may function as a biomarker for evaluating to effects of chemotherapy to this refractory tumor, and patients with BPTF mutation might have a worse prognosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-018-0521-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5816515 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58165152018-02-21 Whole exome sequencing reveals novel somatic alterations in neuroblastoma patients with chemotherapy Duan, Chao Wang, Han Chen, Ying Chu, Ping Xing, Tianyu Gao, Chao Yue, Zhixia Zheng, Jie Jin, Mei Gu, Weiyue Ma, Xiaoli Cancer Cell Int Primary Research BACKGROUND: We ought to explore the acquired somatic alterations, shedding light on genetic basis of somatic alterations in NB patients with chemotherapy. METHODS: Marrow blood samples from NB patients were collected before treatment, after the 2nd and 4th chemotherapy for baseline research and continuous monitoring by whole exome sequencing. Plasma cell free DNA (cfDNA) was prepared for baseline research. Finger nail cells were extracted as self control. The clinical data was analyzed. RESULTS: From December 2014 to February 2016, 27 cases of children with stage IV NB were diagnosed. The follow up time ranged from 5 to 25 months, with a median follow up time of 17 months, 20 patients were stable, one patient died of pulmonary embolism during surgery, six patients died of disease progression. Marrow blood whole exome sequencing demonstrated that several novel somatic mutations were identified in all three trios comply or against the trendy of tumor size variation. Of note, six recurrent mutations in bromodomain PHD finger transcription factor (BPTF) were identified in nine NB patients under the continuous monitoring. The mutation rates variation was positively correlated to tumor size (CC = 0.428, P = 0.021), and patients with BPTF mutation may have a worse prognosis compared with wild type. Meanwhile, CGREF1, CUX2, GP1BA, SLC45A1 and TRA2A were mutated with the trendy oppose as therapeutic effects. The baseline research in three NB patients demonstrated that mutation rate of BPTF, TMCO3, GPRIN2 and C20orf96 in plasma cfDNA were in positive correlation with bone marrow genomic DNA (P = 0.001). CONCLUSIONS: Our study showed that BPTF along with other mutations may function as a biomarker for evaluating to effects of chemotherapy to this refractory tumor, and patients with BPTF mutation might have a worse prognosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-018-0521-3) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-17 /pmc/articles/PMC5816515/ /pubmed/29467591 http://dx.doi.org/10.1186/s12935-018-0521-3 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Primary Research Duan, Chao Wang, Han Chen, Ying Chu, Ping Xing, Tianyu Gao, Chao Yue, Zhixia Zheng, Jie Jin, Mei Gu, Weiyue Ma, Xiaoli Whole exome sequencing reveals novel somatic alterations in neuroblastoma patients with chemotherapy |
title | Whole exome sequencing reveals novel somatic alterations in neuroblastoma patients with chemotherapy |
title_full | Whole exome sequencing reveals novel somatic alterations in neuroblastoma patients with chemotherapy |
title_fullStr | Whole exome sequencing reveals novel somatic alterations in neuroblastoma patients with chemotherapy |
title_full_unstemmed | Whole exome sequencing reveals novel somatic alterations in neuroblastoma patients with chemotherapy |
title_short | Whole exome sequencing reveals novel somatic alterations in neuroblastoma patients with chemotherapy |
title_sort | whole exome sequencing reveals novel somatic alterations in neuroblastoma patients with chemotherapy |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816515/ https://www.ncbi.nlm.nih.gov/pubmed/29467591 http://dx.doi.org/10.1186/s12935-018-0521-3 |
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