Novel insights into molecular patterns of ROS1 fusions in a large Chinese NSCLC cohort: a multicenter study
ROS proto‐oncogene 1, receptor tyrosine kinase (ROS1) rearrangements are a crucial therapeutic target in non‐small cell lung cancer (NSCLC). However, there is limited comprehensive analysis of the molecular patterns of ROS1 fusions. This study aimed to address this gap by analysing 135 ROS1 fusions...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-10-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13509 |
| _version_ | 1827799209812688896 |
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| author | Shengyu Zhou Fayan Zhang Mengxiang Xu Lei Zhang Zhengchuang Liu Qiong Yang Chunyang Wang Baoming Wang Tonghui Ma Jiao Feng |
| author_facet | Shengyu Zhou Fayan Zhang Mengxiang Xu Lei Zhang Zhengchuang Liu Qiong Yang Chunyang Wang Baoming Wang Tonghui Ma Jiao Feng |
| author_sort | Shengyu Zhou |
| collection | DOAJ |
| description | ROS proto‐oncogene 1, receptor tyrosine kinase (ROS1) rearrangements are a crucial therapeutic target in non‐small cell lung cancer (NSCLC). However, there is limited comprehensive analysis of the molecular patterns of ROS1 fusions. This study aimed to address this gap by analysing 135 ROS1 fusions from 134 Chinese NSCLC patients using next‐generation sequencing (NGS). The fusions were categorized into common and uncommon based on their incidence. Our study revealed, for the first time, a unique distribution preference of breakpoints within ROS1, with common fusions occurring in introns 31–33 and uncommon fusions occurring in introns 34 and 35. Additionally, we identified previously unknown breakpoints within intron 28 of ROS1. Furthermore, we identified a close association between the distribution patterns of fusion partners and breakpoints on ROS1, providing important insights into the molecular landscape of ROS1 fusions. We also confirmed the presence of inconsistent breakpoints in ROS1 fusions between DNA‐based NGS and RNA‐based NGS through rigorous validation methods. These inconsistencies were attributed to alternative splicing resulting in out‐of‐frame or exonic ROS1 fusions. These findings significantly contribute to our understanding of the molecular characteristics of ROS1 fusions, which have implications for panel design and the treatment of NSCLC patients with ROS1 rearrangements. |
| first_indexed | 2024-03-11T19:48:20Z |
| format | Article |
| id | doaj.art-461867c2c0c04238a40f9b96b3a12067 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-03-11T19:48:20Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-461867c2c0c04238a40f9b96b3a120672023-10-05T15:36:12ZengWileyMolecular Oncology1574-78911878-02612023-10-0117102200221210.1002/1878-0261.13509Novel insights into molecular patterns of ROS1 fusions in a large Chinese NSCLC cohort: a multicenter studyShengyu Zhou0Fayan Zhang1Mengxiang Xu2Lei Zhang3Zhengchuang Liu4Qiong Yang5Chunyang Wang6Baoming Wang7Tonghui Ma8Jiao Feng9Clinical Nursing Department, School of Nursing and Rehabilitation, Cheeloo College of Medicine Shandong University Jinan ChinaCollege of Traditional Chinese Medicine Shandong University of Traditional Chinese Medicine Jinan ChinaJichenjunchuang Clinical Laboratory Hangzhou ChinaCancer Center, Daping Hospital Army Medical University Chongqing ChinaKey Laboratory of Gastroenterology of Zhejiang Province Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College ChinaGeneral Surgery, Cancer Center Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College) ChinaJichenjunchuang Clinical Laboratory Hangzhou ChinaJichenjunchuang Clinical Laboratory Hangzhou ChinaJichenjunchuang Clinical Laboratory Hangzhou ChinaCancer Center, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College ChinaROS proto‐oncogene 1, receptor tyrosine kinase (ROS1) rearrangements are a crucial therapeutic target in non‐small cell lung cancer (NSCLC). However, there is limited comprehensive analysis of the molecular patterns of ROS1 fusions. This study aimed to address this gap by analysing 135 ROS1 fusions from 134 Chinese NSCLC patients using next‐generation sequencing (NGS). The fusions were categorized into common and uncommon based on their incidence. Our study revealed, for the first time, a unique distribution preference of breakpoints within ROS1, with common fusions occurring in introns 31–33 and uncommon fusions occurring in introns 34 and 35. Additionally, we identified previously unknown breakpoints within intron 28 of ROS1. Furthermore, we identified a close association between the distribution patterns of fusion partners and breakpoints on ROS1, providing important insights into the molecular landscape of ROS1 fusions. We also confirmed the presence of inconsistent breakpoints in ROS1 fusions between DNA‐based NGS and RNA‐based NGS through rigorous validation methods. These inconsistencies were attributed to alternative splicing resulting in out‐of‐frame or exonic ROS1 fusions. These findings significantly contribute to our understanding of the molecular characteristics of ROS1 fusions, which have implications for panel design and the treatment of NSCLC patients with ROS1 rearrangements.https://doi.org/10.1002/1878-0261.13509ChineseDNA‐NGSNSCLCRNA‐NGSROS1 |
| spellingShingle | Shengyu Zhou Fayan Zhang Mengxiang Xu Lei Zhang Zhengchuang Liu Qiong Yang Chunyang Wang Baoming Wang Tonghui Ma Jiao Feng Novel insights into molecular patterns of ROS1 fusions in a large Chinese NSCLC cohort: a multicenter study Molecular Oncology Chinese DNA‐NGS NSCLC RNA‐NGS ROS1 |
| title | Novel insights into molecular patterns of ROS1 fusions in a large Chinese NSCLC cohort: a multicenter study |
| title_full | Novel insights into molecular patterns of ROS1 fusions in a large Chinese NSCLC cohort: a multicenter study |
| title_fullStr | Novel insights into molecular patterns of ROS1 fusions in a large Chinese NSCLC cohort: a multicenter study |
| title_full_unstemmed | Novel insights into molecular patterns of ROS1 fusions in a large Chinese NSCLC cohort: a multicenter study |
| title_short | Novel insights into molecular patterns of ROS1 fusions in a large Chinese NSCLC cohort: a multicenter study |
| title_sort | novel insights into molecular patterns of ros1 fusions in a large chinese nsclc cohort a multicenter study |
| topic | Chinese DNA‐NGS NSCLC RNA‐NGS ROS1 |
| url | https://doi.org/10.1002/1878-0261.13509 |
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