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Genetic Mutation Analysis in Small Cell Lung Cancer by a Novel NGS-Based Targeted Resequencing Gene Panel and Relation with Clinical Features

BACKGROUND: Small cell lung cancer (SCLC) is an aggressive and invasive malignancy that presents at advanced clinical stage with no more effective treatments. Development of a method for its early detection would be useful, also new therapeutic target need to be discovered; however, there is a lack...

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Autores principales: Jin, Wang, Lei, Zhao, Xu, Sun, Fachen, Zhou, Yixiang, Zhang, Shilei, Zhao, Tao, Guo, Zhe, Sun, Fengzhou, Li, Su, Wen-Hui, Chundong, Gu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046547/
https://www.ncbi.nlm.nih.gov/pubmed/33880365
http://dx.doi.org/10.1155/2021/3609028
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author Jin, Wang
Lei, Zhao
Xu, Sun
Fachen, Zhou
Yixiang, Zhang
Shilei, Zhao
Tao, Guo
Zhe, Sun
Fengzhou, Li
Su, Wen-Hui
Chundong, Gu
author_facet Jin, Wang
Lei, Zhao
Xu, Sun
Fachen, Zhou
Yixiang, Zhang
Shilei, Zhao
Tao, Guo
Zhe, Sun
Fengzhou, Li
Su, Wen-Hui
Chundong, Gu
author_sort Jin, Wang
collection PubMed
description BACKGROUND: Small cell lung cancer (SCLC) is an aggressive and invasive malignancy that presents at advanced clinical stage with no more effective treatments. Development of a method for its early detection would be useful, also new therapeutic target need to be discovered; however, there is a lack of information about its oncogenic driver gene mutations. OBJECTIVES: We aim to identify the SCLC-related genomic variants that associate with clinical staging and serum protein biomarkers observed in other types of lung cancer. METHODS: We screened formalin-fixed paraffin-embedded (FFPE) biopsy tissues of 32 Chinese SCLC patients using the 303 oncogenic driver gene panel generated by Tiling PCR amplification sequencing (tPAS) and analyzed the patients' corresponding serum protein levels of CYFRA21-1 CEA, NSE, and SCCA. RESULTS: In total, we found 147 SCLC-related mutant genes, among these, three important genes (TP53, RB1, KMT2D) as well as five novel genes LRRK2, BRCA1, PTCH1, ARID2, and APC that altogether occurred in 90% of patients. Furthermore, increased mutations to 6 genes (WT1, NOTCH1, EPHA3, KDM6A, SETD2, ACVR1B) significantly associated with higher serum NSE levels (P = 0.0016) and higher clinical stages II + III compared to stage I (P = 0.06). CONCLUSIONS: Our panel is relatively reliable in detecting the oncogenic mutations of Chinese SCLC patients. Based on our findings, it may be possible to combine SCLC-related mutations and serum NSE for a simple detection of clinical staging.
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spelling pubmed-80465472021-04-19 Genetic Mutation Analysis in Small Cell Lung Cancer by a Novel NGS-Based Targeted Resequencing Gene Panel and Relation with Clinical Features Jin, Wang Lei, Zhao Xu, Sun Fachen, Zhou Yixiang, Zhang Shilei, Zhao Tao, Guo Zhe, Sun Fengzhou, Li Su, Wen-Hui Chundong, Gu Biomed Res Int Research Article BACKGROUND: Small cell lung cancer (SCLC) is an aggressive and invasive malignancy that presents at advanced clinical stage with no more effective treatments. Development of a method for its early detection would be useful, also new therapeutic target need to be discovered; however, there is a lack of information about its oncogenic driver gene mutations. OBJECTIVES: We aim to identify the SCLC-related genomic variants that associate with clinical staging and serum protein biomarkers observed in other types of lung cancer. METHODS: We screened formalin-fixed paraffin-embedded (FFPE) biopsy tissues of 32 Chinese SCLC patients using the 303 oncogenic driver gene panel generated by Tiling PCR amplification sequencing (tPAS) and analyzed the patients' corresponding serum protein levels of CYFRA21-1 CEA, NSE, and SCCA. RESULTS: In total, we found 147 SCLC-related mutant genes, among these, three important genes (TP53, RB1, KMT2D) as well as five novel genes LRRK2, BRCA1, PTCH1, ARID2, and APC that altogether occurred in 90% of patients. Furthermore, increased mutations to 6 genes (WT1, NOTCH1, EPHA3, KDM6A, SETD2, ACVR1B) significantly associated with higher serum NSE levels (P = 0.0016) and higher clinical stages II + III compared to stage I (P = 0.06). CONCLUSIONS: Our panel is relatively reliable in detecting the oncogenic mutations of Chinese SCLC patients. Based on our findings, it may be possible to combine SCLC-related mutations and serum NSE for a simple detection of clinical staging. Hindawi 2021-04-05 /pmc/articles/PMC8046547/ /pubmed/33880365 http://dx.doi.org/10.1155/2021/3609028 Text en Copyright © 2021 Wang Jin et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Jin, Wang
Lei, Zhao
Xu, Sun
Fachen, Zhou
Yixiang, Zhang
Shilei, Zhao
Tao, Guo
Zhe, Sun
Fengzhou, Li
Su, Wen-Hui
Chundong, Gu
Genetic Mutation Analysis in Small Cell Lung Cancer by a Novel NGS-Based Targeted Resequencing Gene Panel and Relation with Clinical Features
title Genetic Mutation Analysis in Small Cell Lung Cancer by a Novel NGS-Based Targeted Resequencing Gene Panel and Relation with Clinical Features
title_full Genetic Mutation Analysis in Small Cell Lung Cancer by a Novel NGS-Based Targeted Resequencing Gene Panel and Relation with Clinical Features
title_fullStr Genetic Mutation Analysis in Small Cell Lung Cancer by a Novel NGS-Based Targeted Resequencing Gene Panel and Relation with Clinical Features
title_full_unstemmed Genetic Mutation Analysis in Small Cell Lung Cancer by a Novel NGS-Based Targeted Resequencing Gene Panel and Relation with Clinical Features
title_short Genetic Mutation Analysis in Small Cell Lung Cancer by a Novel NGS-Based Targeted Resequencing Gene Panel and Relation with Clinical Features
title_sort genetic mutation analysis in small cell lung cancer by a novel ngs-based targeted resequencing gene panel and relation with clinical features
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046547/
https://www.ncbi.nlm.nih.gov/pubmed/33880365
http://dx.doi.org/10.1155/2021/3609028
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