A novel SETD3-ALK fusion in lung adenocarcinoma and sustained clinical response to crizotinib. (January 2023)

• Record Type: Journal Article
• Authors: Dai, Shuang; Liu, Xiao-Qin; Wu, Qiang; Du, Chun-Mei; Liu, Qing; Xue, Yin-Yin; Luo, Feng; Li, Yan
• Is Part Of: Lung cancer. Volume 175(2023)
• Page Start: 121
• Page End: 124
• Publication Date: 2023-01
• Subjects: Lung adenocarcinoma -- SETD3-ALK -- Crizotinib -- Next-generation sequencing (NGS); ALK Anaplastic lymphoma kinase -- NSCLC Non-small cell lung cancer -- LUAD Lung adenocarcinoma -- SETD3 SET domain containing 3 -- CT Computed tomography -- IHC Immunohistochemical -- NGS Next-generation sequencing -- PFS Progression-free survival -- TKI Tyrosine kinase inhibitor -- TTF1 Thyroid transcription factor 1 -- CEA Carcinoembryonic antigen; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2022.11.020
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: SETD3-ALK (S6:A20) has never been reported previously. First report about long-term benefit to crizotinib for SETD3-ALK fusion. NGS could detect all of ALK fusion subtypes simultaneously, providing guided therapeutic clues. Abstract: Objectives: Anaplastic lymphoma kinase (ALK) rearrangement is a vital driving mutation in non-small cell lung cancer (NSCLC). ALK rearrangements may involve different breakpoints and multiple fusion partners, presenting different therapeutic responses. There are no standard treatment options for rare ALK rearrangements. Here, we report a case of advanced lung adenocarcinoma (LUAD) harboring a novel SET domain containing 3 (SETD3)-ALK fusion and sensitive to crizotinib, which has not been previously reported. Materials and methods: Molecular and pathological features were confirmed using percutaneous lung biopsy guided by computed tomography (CT), immunohistochemical (IHC) staining and next-generation sequencing (NGS). Results: NGS revealed that a novel SETD3-ALK fusion was detected in the patient with LUAD, and IHC analysis confirmed that this fusion had functional expression. The patient had a progression-free survival (PFS) over 16 months after crizotinib treatment (250 mg b.i.d.), with ongoing clinical response. Conclusion: This case introduces a novel and meaningful ALK fusion type in LUAD with sustained sensitivity to crizotinib, providing a reference to the treatment of similar cases with SETD3-ALK fusion in the future.