title: TPD52L1-ROS1, a new ROS1 fusion variant in lung adenosquamous cell carcinoma identified by comprehensive genomic profiling.
abstract: Crizotinib was approved for the treatment of ROS1-rearranged non-small cell lung cancer (NSCLC) patients in the US on 11 March, 2016. Interestingly no one companion diagnostic test (CDx) has been approved simultaneously with this approval of crizotinib. Hence, an ideal and adequate CDx will have to be able to identify ROS1 fusions without the knowledge of the fusion partners to ROS1, and as to date there are 13 fusion partners reported for ROS1 in NSCLC. Here we report a novel TPD52L1-ROS1 fusion variant in NSCLC. This novel TPD52L1-ROS1 fusion variant is generated by the fusion of exons 1-3 of TPD52L1 on chromosome 6q22-23 to the exons 33-43 of ROS1 on chromosome 6q22, likely from an intra-chromosomal deletion and subsequent fusion event similar to the generation of EML4-ALK. The predicted TPD52L1-ROS1 protein product contains 655 amino acids comprising of the N-terminal amino acids 1-95 of TPD52L1 and C-terminal amino acids of 1789-2348 of ROS1. In summary, TPD52L1-ROS1 is a novel ROS1 fusion variant in NSCLC identified by comprehensive genomic profiling and should be included in any ROS1 detecting assays that depend on identifying the corresponding fusion partners, such as reverse transcriptase-polymerase chain reaction (RT-PCR).
authors.affiliation: University Oncology Associates, Section of Hematology and Oncology, Department of Medicine, University of California, San Francisco-Fresno, Fresno, CA 93701, United States. Electronic address: vzhu@fresno.ucsf.edu.
authors.forename: Viola Weijia
authors.initials: VW
authors.lastname: Zhu
authors.affiliation: University Pulmonary Associates, Section of Pulmonary and Critical Care, Department of Medicine, University of California, San Francisco-Fresno, Fresno, CA 93701, United States.
authors.forename: Daya
authors.initials: D
authors.lastname: Upadhyay
authors.affiliation: Foundation Medicine, Inc., 150 Second Street, Cambridge, MA 02141, United States.
authors.forename: Alexa B
authors.initials: AB
authors.lastname: Schrock
authors.affiliation: Foundation Medicine, Inc., 150 Second Street, Cambridge, MA 02141, United States.
authors.forename: Kyle
authors.initials: K
authors.lastname: Gowen
authors.affiliation: Foundation Medicine, Inc., 150 Second Street, Cambridge, MA 02141, United States.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Chao Family Comprehensive Cancer Center, Department of Medicine, Division of Hematology-Oncology, University of California, Irvine School of Medicine, Orange, CA 92868, United States.
authors.forename: Sai-Hong Ignatius
authors.initials: SH
authors.lastname: Ou
mesh_terms: D000368:Aged; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D059186:Chemoradiotherapy, Adjuvant; D000077547:Crizotinib; D005091:Exons; D023281:Genomics / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging* / Q000188:drug therapy; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use
chemical_list: D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011720:Pyrazoles; D011725:Pyridines; C486416:TPD52L1 protein, human; D000077547:Crizotinib; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human
keywords: Comprehensive genomic profiling; Intra-chromosomal deletion; ROS1-rearranged NSCLC; TPD52L1-ROS1