{"doi":"10.1002/1878-0261.13509","title":"Novel insights into molecular patterns of <i>ROS1</i> fusions in a large Chinese <scp>NSCLC</scp> cohort: a multicenter study","abstract":"<jats:p>ROS proto‐oncogene 1, receptor tyrosine kinase (<jats:italic>ROS1</jats:italic>) rearrangements are a crucial therapeutic target in non‐small cell lung cancer (NSCLC). However, there is limited comprehensive analysis of the molecular patterns of <jats:italic>ROS1</jats:italic> fusions. This study aimed to address this gap by analysing 135 <jats:italic>ROS1</jats:italic> 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 <jats:italic>ROS1</jats:italic>, 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 <jats:italic>ROS1</jats:italic>. Furthermore, we identified a close association between the distribution patterns of fusion partners and breakpoints on <jats:italic>ROS1</jats:italic>, providing important insights into the molecular landscape of <jats:italic>ROS1</jats:italic> fusions. We also confirmed the presence of inconsistent breakpoints in <jats:italic>ROS1</jats:italic> 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 <jats:italic>ROS1</jats:italic> fusions. These findings significantly contribute to our understanding of the molecular characteristics of <jats:italic>ROS1</jats:italic> fusions, which have implications for panel design and the treatment of NSCLC patients with <jats:italic>ROS1</jats:italic> rearrangements.</jats:p>","journal":"Molecular Oncology","year":2023,"id":593230,"datarank":0.5089097407551474,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.13617374328694726,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.13617374328694726,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":6,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1518338,"name":"Fayan Zhang","orcid":null,"position":1,"is_corresponding":false},{"id":1518339,"name":"Mengxiang Xu","orcid":null,"position":2,"is_corresponding":false},{"id":285902,"name":"Lei Zhang","orcid":"0000-0002-7704-5237","position":3,"is_corresponding":false},{"id":1518340,"name":"Zhengchuang Liu","orcid":null,"position":4,"is_corresponding":false},{"id":470993,"name":"Qiong Yang","orcid":"0000-0002-2442-2094","position":5,"is_corresponding":false},{"id":160847,"name":"Chunyang Wang","orcid":"0000-0001-9694-5831","position":6,"is_corresponding":false},{"id":1518341,"name":"Baoming Wang","orcid":null,"position":7,"is_corresponding":false},{"id":1518342,"name":"Tonghui Ma","orcid":"0000-0002-5414-0522","position":8,"is_corresponding":false},{"id":1518343,"name":"Jiao Feng","orcid":"0000-0001-6128-851X","position":9,"is_corresponding":false},{"id":976832,"name":"Shengyu Zhou","orcid":"0000-0002-6254-2986","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Novel insights into molecular patterns of <i>ROS1</i> fusions in a large Chinese <scp>NSCLC</scp> cohort: a multicenter study","abstract":"<jats:p>ROS proto‐oncogene 1, receptor tyrosine kinase (<jats:italic>ROS1</jats:italic>) rearrangements are a crucial therapeutic target in non‐small cell lung cancer (NSCLC). However, there is limited comprehensive analysis of the molecular patterns of <jats:italic>ROS1</jats:italic> fusions. This study aimed to address this gap by analysing 135 <jats:italic>ROS1</jats:italic> 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 <jats:italic>ROS1</jats:italic>, 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 <jats:italic>ROS1</jats:italic>. Furthermore, we identified a close association between the distribution patterns of fusion partners and breakpoints on <jats:italic>ROS1</jats:italic>, providing important insights into the molecular landscape of <jats:italic>ROS1</jats:italic> fusions. We also confirmed the presence of inconsistent breakpoints in <jats:italic>ROS1</jats:italic> 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 <jats:italic>ROS1</jats:italic> fusions. These findings significantly contribute to our understanding of the molecular characteristics of <jats:italic>ROS1</jats:italic> fusions, which have implications for panel design and the treatment of NSCLC patients with <jats:italic>ROS1</jats:italic> rearrangements.</jats:p>","is_dataset_classified":null,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37584407","pmcid":"PMC10552890","openalex_id":"https://openalex.org/W4385850889","authors":[],"funders":[{"funder_name":"Zhejiang Province Medical and Health Research Projects","grant_id":"2016KYB027","title":null},{"funder_name":"Zhejiang Province Medical and Health Research Projects","grant_id":"2017KY010","title":null}],"total_grants":2,"fwci":1.832,"citation_percentile":0.86493166,"influential_citations":0,"citation_trend":[{"year":2024,"count":2},{"year":2025,"count":7},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1878-0261.13509","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1878-0261.13509","host_type":"publisher"},{"url":"https://febs.onlinelibrary.wiley.com/doi/pdf/10.1002/1878-0261.13509","host_type":"publisher"},{"url":"https://doi.org/10.1002/1878-0261.13509","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37584407","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10552890","host_type":"repository"},{"url":"https://doaj.org/article/461867c2c0c04238a40f9b96b3a12067","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10552890/pdf/MOL2-17-2200.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10552890","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10552890?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Lung Cancer Treatments and Mutations","Cancer Genomics and Diagnostics","RNA and protein synthesis mechanisms"],"mesh_terms":["Proto-Oncogene Mas","East Asian People","Adult","Aged","Carcinoma, Non-Small-Cell Lung","China","Female","Humans","Lung Neoplasms","Male","Middle Aged","Protein-Tyrosine Kinases","Proto-Oncogene Proteins","Cohort Studies","Oncogene Proteins, Fusion","Asian People","High-Throughput Nucleotide Sequencing"],"keywords":["ROS1","splice","Exon","Biology","Breakpoint","Computational biology","Genetics","Cancer research","Alternative splicing","Intron","Cancer","Gene","Adenocarcinoma","Chinese","NSCLC","Dna-ngs","Rna-ngs"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-26T17:54:15.946569Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}