ArticleBMC medicine2022
Reliability analysis of exonic-breakpoint fusions identified by DNA sequencing for predicting the efficacy of targeted therapy in non-small cell lung cancer.
Article in BMC medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 22 citations in OpenAlex.
- Clinically actionable stratification of uncommon MET fusions: a precision oncology framework.Journal of translational medicine · 2026Article
- Illuminating the FGFR fusion landscape in Chinese patients: unveiling novel molecular insights and clinical implications.The oncologist · 2025Article
- Unveiling the BRAF fusion structure variations through DNA and RNA sequencing.British journal of cancer · 2025Article
- Analytical validation of Aspyre Clinical Test for Lung (Blood): A multiplexed PCR and pyrophosphorolysis-based assay for detecting actionable NSCLC variants in plasma cfDNA and cfRNA.The journal of liquid biopsy · 2025Article
- Combined utility of genomic breakpoints and frame is a reliable predictor of ALK transcript function.Scientific reports · 2025Article
- Actionable Structural Variant Detection via RNA-NGS and DNA-NGS in Patients With Advanced Non-Small Cell Lung Cancer.JAMA network open · 2024Article
- Clinical and Molecular Traits of a Novel SPECC1L-ALK Fusion in a Patient with Advanced Non-Small Cell Lung Cancer.Journal of personalized medicine · 2024Article
- ASPYRE-Lung: validation of a simple, fast, robust and novel method for multi-variant genomic analysis of actionable NSCLC variants in FFPE tissue.Frontiers in oncology · 2024Article
- [Chinese Expert Consensus on the Clinical Practice of Non-small Cell Lung Cancer Fusion Gene Detection Based on RNA-based NGS].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- A unified DNA- and RNA-based NGS strategy for the analysis of multiple types of variants at the dual nucleic acid level in solid tumors.Journal of clinical laboratory analysis · 2023Article
- Decoding Oncofusions: Unveiling Mechanisms, Clinical Impact, and Prospects for Personalized Cancer Therapies.Cancers · 2023Review
- Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy in NSCLC.Frontiers of medicine · 2023Article
- Molecular characterization of genomic breakpoints of ALK rearrangements in non-small cell lung cancer.Molecular oncology · 2023Article
- Case Report: Efficacy of ensartinib treatment in pulmonary inflammatory myofibroblastic tumor with a rareFrontiers in oncology · 2022Article
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7 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundDiverse genomic breakpoints of fusions that localize to intronic, exonic, or intergenic regions have been identified by DNA next-generation sequencing (NGS), but the role of exonic breakpoints remains elusive. We investigated whether exonic-breakpoint fusions could predict matched targeted therapy efficacy in non-small cell lung cancer (NSCLC).
methodsNSCLC samples were analyzed by DNA NGS, RNA NGS, immunohistochemistry (IHC), and fluorescence in situ hybridization.
resultsUsing DNA NGS, kinase fusions were identified in 685 of 7148 (9.6%) NSCLCs, with 74 harboring exonic-breakpoint fusions, mostly anaplastic lymphoma kinase (ALK) fusions. RNA NGS and IHC revealed that 11 of 55 (20%) exonic-breakpoint fusions generated no aberrant transcript/protein, possibly due to open reading frame disruption or different gene transcriptional orientations. Four cases of genomic-positive but RNA/protein-negative fusions were treated with matched targeted therapy, but progressive disease developed within 2 months. Nevertheless, 44 of 55 (80%) exonic-breakpoint fusions produced chimeric transcripts/proteins, possibly owing to various alternative splicing patterns, including exon skipping, alternative splice site selection, and intron retention. Most of these genomic- and RNA/protein-positive fusion cases showed a clinical response to matched targeted therapy. Particularly, there were no differences in objective response rate (P = 0.714) or median progression-free survival (P = 0.500) between intronic-breakpoint (n = 56) and exonic-breakpoint ALK fusion subtypes (n = 11) among ALK RNA/protein-validated patients who received first-line crizotinib.
conclusionsExonic-breakpoint fusions may generate in-frame fusion transcripts/proteins or not, and thus are unreliable for predicting the efficacy of targeted therapy, which highlights the necessity of implementing RNA or protein assays for functional validation in exonic-breakpoint fusion cases.
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