ArticleJournal of translational medicine2021
Molecular characteristics and clinical outcomes of complex ALK rearrangements identified by next-generation sequencing in non-small cell lung cancers.
Article in Journal of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- Treatment of an Advanced NSCLC Patient with a Rare OSBPL9-ALK Fusion: A Case Report.Healthcare (Basel, Switzerland) · 2026Article
- First-Line Lorlatinib in Striatin-Anaplastic Lymphoma Kinase-Positive Lung Adenocarcinoma: A Case Report and Literature Review.Respirology case reports · 2026Article
- Beyond EML4: efficacy of targeted therapy in lung cancer patients with rare ALK fusions - a real-world retrospective analysis.NPJ precision oncology · 2026Article
- Review
- Refining Criteria for Choosing the First-Line Treatment for Real-World Patients with AdvancedInternational journal of molecular sciences · 2025Review
- The fusion characteristics of RET fusion in pan-cancer among the Chinese population: A comprehensive genomic analysis.Translational oncology · 2025Article
- The long-term avoided recurrences and recurrence-related cost of alectinib for postoperative adjuvant therapy in Chinese patients with early-stage ALK-positive non-small cell lung cancer.Frontiers in public health · 2025Article
- Actionable Structural Variant Detection via RNA-NGS and DNA-NGS in Patients With Advanced Non-Small Cell Lung Cancer.JAMA network open · 2024Article
- Article
- Clinical difference on the variants and co-mutation in a Chinese cohort with ALK-positive advanced non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Reclassification of a spindle cell sarcoma after identification of a TFG-ROS1 fusion: A case demonstrating the clinical benefit of next-generation sequencing in sarcoma.Molecular genetics & genomic medicine · 2024Article
- Review
- Case Report: Structurally RareOncoTargets and therapy · 2024Article
- Redefining Recovery: The Transformative Impact of the ALINA Trial on Adjuvant Therapy forLung Cancer (Auckland, N.Z.) · 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
- Superior clinical outcomes in patients with non-small cell lung cancer harboring multipleTranslational lung cancer research · 2023Article
- Molecular characterization of genomic breakpoints of ALK rearrangements in non-small cell lung cancer.Molecular oncology · 2023Article
- A novel intergenic region (chr2: 30,193,816)-ALK fusion shows sensitivity to Alectinib in lung adenocarcinoma.BMC pulmonary medicine · 2023Article
- Identification and therapeutic evaluation of ALK rearrangements in non-small-cell lung cancer.The journal of pathology. Clinical research · 2022Article
- Molecular Profiling in Non-Squamous Non-Small Cell Lung Carcinoma: Towards a Switch to Next-Generation Sequencing Reflex Testing.Journal of personalized medicine · 2022Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundComplex kinase rearrangement, a mutational process involving one or two chromosomes with clustered rearrangement breakpoints, interferes with the accurate detection of kinase fusions by DNA-based next-generation sequencing (NGS). We investigated the characteristics of complex ALK rearrangements in non-small cell lung cancers using multiple molecular tests.
methodsSamples of non-small cell lung cancer patients were analyzed by targeted-capture DNA-based NGS with probes tilling the selected intronic regions of fusion partner genes, RNA-based NGS, RT-PCR, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
resultsIn a large cohort of 6576 non-small cell lung cancer patients, 343 (5.2%) cases harboring ALK rearrangements were identified. Fourteen cases with complex ALK rearrangements were identified by DNA-based NGS and classified into three types by integrating various genomic features, including intergenic (n = 3), intragenic (n = 5) and "bridge joint" rearrangements (n = 6). All thirteen cases with sufficient samples actually expressed canonical EML4-ALK fusion transcripts confirmed by RNA-based NGS. Besides, positive ALK IHC was detected in 13 of 13 cases, and 9 of 11 cases were positive in FISH testing. Patients with complex ALK rearrangements who received ALK inhibitors treatment (n = 6), showed no difference in progression-free survival (PFS) compared with patients with canonical ALK fusions n = 36, P = 0.9291).
conclusionsThis study firstly reveals the molecular characteristics and clinical outcomes of complex ALK rearrangements in NSCLC, sensitive to ALK inhibitors treatment, and highlights the importance of utilizing probes tilling the selected intronic regions of fusion partner genes in DNA-based NGS for accurate fusion detection. RNA and protein level assay may be critical in validating the function of complex ALK rearrangements in clinical practice for optimal treatment decision.
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