title: Identification of atypical ATRNL1 insertion to EML4-ALK fusion gene in NSCLC.
abstract: We herein present a rare case of an EML4-ALK positive patient. A 61-year-old man was diagnosed with locoregional non-small cell lung cancer (NSCLC). No EGFR mutations were detected, and therefore the ALK rearrangement was evaluated using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and the reverse transcription PCR (RT-PCR) method for EML4-ALK. All methods showed a positive result and, therefore, the patient was treated with crizotinib with a good therapeutic response. However, a detailed RT-PCR analysis and sequencing revealed an unexpected 138 bp insertion of attractin-like 1 (ATRNL1) gene into the EML4-ALK fusion gene. In our case, the positive therapeutic response suggests that ATRNL1 insertion does not affect EML4-ALK's sensitivity to crizotinib. This case shows great EML4-ALK heterogeneity and also that basic detection methods (IHC, FISH) cannot fully specify ALK rearrangement but in many cases a full specification seems to be important for an effective TKI indication, and sequencing ALK variants might contribute to optimized patient selection.
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic. Electronic address: blanka.robesova@fnbrno.cz.
authors.forename: Blanka
authors.initials: B
authors.lastname: Robesova
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Bajerova
authors.affiliation: Department of Pathology, Masaryk University and University Hospital Brno, Brno, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Hausnerova
authors.affiliation: Department of Respiratory Diseases and Tuberculosis, Masaryk University and University Hospital Brno, Brno, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Skrickova
authors.affiliation: Department of Respiratory Diseases and Tuberculosis, Masaryk University and University Hospital Brno, Brno, Czech Republic.
authors.forename: Marcela
authors.initials: M
authors.lastname: Tomiskova
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Dvorakova
mesh_terms: D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D000077547:Crizotinib; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D013902:Radiography, Thoracic; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome
chemical_list: C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib
keywords: ATRNL1; Crizotinib; EML4-ALK; Lung cancer; NSCLC; Targeted therapy