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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
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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. |
format | Online Article Text |
id | pubmed-8046547 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
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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