Abstract
The purpose of the study is to investigate the constitution of anaplastic lymphoma kinase (ALK) fusion variants in East Asian lung adenocarcinoma (LUAC) patients and to provide instructional data for the variants that should be included in the companion diagnostic assay to screen for ALK positive patients. From June 2014 to August 2015, 158 ALK fusion positive formalin-fixed, paraffin-embedded (FFPE) samples were identified, including 3 patient-derived xenograft (PDX) tissues and 155 resected or fine needle aspiration (FNA) tissues, all derived from Korean or Chinese patients. Either purified RNA or crude tissue lysate from the 158 FFPE samples were analyzed by NanoString nCounter Elements assay with a multiplexed probe mix in a single tube targeting ALK fusion transcripts including 29 known variants. Of the total 158 ALK fusion positive samples, 133 samples harbored echinoderm microtubule-associated protein-like 4 ALK (EML4-ALK) fusion, 4 samples harbored Kinesin Family Member 5B ALK (KIF5B-ALK) fusion, 4 samples harbored huntingtin interacting protein 1 ALK (HIP1-ALK) fusion, 1 sample harbored kinesin light chain 1 ALK (KLC1-ALK) fusion, and the remaining 16 samples harbored novel fusion variants. Of the 133 EML4-ALK positive samples, 55 samples harbored E13:A20 variants (Variant 1), 55 samples harbored E6:A20 (Variant 3), 16 samples harbored E20:A20 (Variant 2), 4 samples harbored E18:A20 and 3 samples harbored E2:A20. This is the largest molecular epidemiological study to describe ALK fusion variants in East Asian LUAC patients. EML4 is the most common fusion partner of ALK gene. About 84% of ALK fusion positive patients harbor EML4-ALK, and 5.7% harbor non-EML4-ALK fusions. The remaining 10% harbor fusions with unknown partners. For EML4-ALK, E13:A20 and E6:A20 are the most common variants, comprising more than 80% of EML4-ALK fusion. E20:A20, E18:A20 and E2:A20 are also identified in East Asian patients. The constitution of EML4-ALK fusion variants is similar to the previous reports of patient cohorts in western countries. All the ALK fusion variants mentioned should be included in the LUAC fusion screening assays.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
