TPD52L1-ROS1, a new ROS1 fusion variant in lung adenosquamous cell carcinoma identified by comprehensive genomic profiling. (July 2016)

• Record Type: Journal Article
• Authors: Zhu, Viola Weijia; Upadhyay, Daya; Schrock, Alexa B.; Gowen, Kyle; Ali, Siraj M.; Ou, Sai-Hong Ignatius
• Is Part Of: Lung cancer. Volume 97(2016)
• Page Start: 48
• Page End: 50
• Publication Date: 2016-07
• Subjects: TPD52L1-ROS1 -- ROS1-rearranged NSCLC -- Comprehensive genomic profiling -- Intra-chromosomal deletion; 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.2016.04.013
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: TPD52L1-ROS1 : new ROS1 -rearranged NSCLC variant. Contains coiled-coil domain. Generated from intra-chromosomal deletion/fusion. 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).