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Molecular subtyping of small‐cell lung cancer based on mutational signatures with different genomic features and therapeutic strategies
Small‐cell lung cancer (SCLC) is an exceptionally lethal malignancy characterized by extremely high alteration rates and tumor heterogeneity, which limits therapeutic options. In contrast to non‐small‐cell lung cancer that develops rapidly with precision oncology, SCLC still remains outside the real...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9899606/ https://www.ncbi.nlm.nih.gov/pubmed/36178064 http://dx.doi.org/10.1111/cas.15606 |
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author | Wang, Haiyong Wu, Shuangxiu Li, Zhenzhen Zhang, Chenyue Shang, Xiaoling Zhao, Chenglong Li, Zhenxiang Lin, Jiamao Guo, Jun Wang, Zhehai |
author_facet | Wang, Haiyong Wu, Shuangxiu Li, Zhenzhen Zhang, Chenyue Shang, Xiaoling Zhao, Chenglong Li, Zhenxiang Lin, Jiamao Guo, Jun Wang, Zhehai |
author_sort | Wang, Haiyong |
collection | PubMed |
description | Small‐cell lung cancer (SCLC) is an exceptionally lethal malignancy characterized by extremely high alteration rates and tumor heterogeneity, which limits therapeutic options. In contrast to non‐small‐cell lung cancer that develops rapidly with precision oncology, SCLC still remains outside the realm of precision medicine. No recurrent and actionable mutations have been detected. Additionally, a paucity of substantive tumor specimens has made it even more difficult to classify SCLC subtypes based on genetic background. We therefore carried out whole‐exome sequencing (WES) on the largest available Chinese SCLC cohort. For the first time, we partitioned SCLC patients into three clusters with different genomic alteration profiles and clinical features based on their mutational signatures. We showed that these clusters presented differences in intratumor heterogeneity and genome instability. Moreover, a wide existence of mutually exclusive gene alterations, typically within similar biological functions, was detected and suggested a high SCLC intertumoral heterogeneity. Particularly, Cluster 1 presented the greatest potential to benefit from immunotherapy, and Cluster 3 constituted recalcitrant SCLC, warranting biomarker‐directed drug development and targeted therapies in clinical trials. Our study would provide an in‐depth insight into the genome characteristics of the Chinese SCLC cohort, defining distinct molecular subtypes as well as subtype‐specific therapies and biomarkers. We propose tailoring differentiated therapies for distinct molecular subgroups, centering on a personalized precision chemotherapy strategy combined with immunization or targeted therapy for patients with SCLC. |
format | Online Article Text |
id | pubmed-9899606 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98996062023-02-09 Molecular subtyping of small‐cell lung cancer based on mutational signatures with different genomic features and therapeutic strategies Wang, Haiyong Wu, Shuangxiu Li, Zhenzhen Zhang, Chenyue Shang, Xiaoling Zhao, Chenglong Li, Zhenxiang Lin, Jiamao Guo, Jun Wang, Zhehai Cancer Sci ORIGINAL ARTICLES Small‐cell lung cancer (SCLC) is an exceptionally lethal malignancy characterized by extremely high alteration rates and tumor heterogeneity, which limits therapeutic options. In contrast to non‐small‐cell lung cancer that develops rapidly with precision oncology, SCLC still remains outside the realm of precision medicine. No recurrent and actionable mutations have been detected. Additionally, a paucity of substantive tumor specimens has made it even more difficult to classify SCLC subtypes based on genetic background. We therefore carried out whole‐exome sequencing (WES) on the largest available Chinese SCLC cohort. For the first time, we partitioned SCLC patients into three clusters with different genomic alteration profiles and clinical features based on their mutational signatures. We showed that these clusters presented differences in intratumor heterogeneity and genome instability. Moreover, a wide existence of mutually exclusive gene alterations, typically within similar biological functions, was detected and suggested a high SCLC intertumoral heterogeneity. Particularly, Cluster 1 presented the greatest potential to benefit from immunotherapy, and Cluster 3 constituted recalcitrant SCLC, warranting biomarker‐directed drug development and targeted therapies in clinical trials. Our study would provide an in‐depth insight into the genome characteristics of the Chinese SCLC cohort, defining distinct molecular subtypes as well as subtype‐specific therapies and biomarkers. We propose tailoring differentiated therapies for distinct molecular subgroups, centering on a personalized precision chemotherapy strategy combined with immunization or targeted therapy for patients with SCLC. John Wiley and Sons Inc. 2022-10-28 /pmc/articles/PMC9899606/ /pubmed/36178064 http://dx.doi.org/10.1111/cas.15606 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | ORIGINAL ARTICLES Wang, Haiyong Wu, Shuangxiu Li, Zhenzhen Zhang, Chenyue Shang, Xiaoling Zhao, Chenglong Li, Zhenxiang Lin, Jiamao Guo, Jun Wang, Zhehai Molecular subtyping of small‐cell lung cancer based on mutational signatures with different genomic features and therapeutic strategies |
title | Molecular subtyping of small‐cell lung cancer based on mutational signatures with different genomic features and therapeutic strategies |
title_full | Molecular subtyping of small‐cell lung cancer based on mutational signatures with different genomic features and therapeutic strategies |
title_fullStr | Molecular subtyping of small‐cell lung cancer based on mutational signatures with different genomic features and therapeutic strategies |
title_full_unstemmed | Molecular subtyping of small‐cell lung cancer based on mutational signatures with different genomic features and therapeutic strategies |
title_short | Molecular subtyping of small‐cell lung cancer based on mutational signatures with different genomic features and therapeutic strategies |
title_sort | molecular subtyping of small‐cell lung cancer based on mutational signatures with different genomic features and therapeutic strategies |
topic | ORIGINAL ARTICLES |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9899606/ https://www.ncbi.nlm.nih.gov/pubmed/36178064 http://dx.doi.org/10.1111/cas.15606 |
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