Identification of a novel TMEM106B-ROS1 fusion variant in lung adenocarcinoma by comprehensive genomic profiling. Issue 3 (June 2015)

• Record Type: Journal Article
• Authors: Ou, Sai-Hong Ignatius; Chalmers, Zachary R.; Azada, Michele C.; Ross, Jeffrey S.; Stephens, Philip J.; Ali, Siraj M.; Miller, Vincent A.
• Is Part Of: Lung cancer. Volume 88:Issue 3(2015:Jun.)
• Page Start: 352
• Page End: 354
• Publication Date: 2015-06
• Subjects: 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.2015.03.014
• Languages: English
• ISSNs: 0169-5002

Abstract

<abstract abstract-type="author" id="abs0005"> <title id="sect0005">Abstract</title> <sec> <title id="sect0010">Objectives</title> <p id="spar0005"> <italic>ROS1</italic>-rearranged non-small cell lung cancer (NSCLC) is a unique molecularly defined yet heterogeneous subset of NSCLC. To date 12 known fusion partners of <italic>ROS1</italic> in NSCLC have been reported. While crizotinib, a multi-targeted ALK/ROS1/MET tyrosine kinase inhibitor (TKI), has demonstrated significant clinical activity in <italic>ROS1</italic>-rearranged NSCLC, no companion diagnostic assay has been approved for the detection of <italic>ROS1</italic>-rearrange NSCLC by the US FDA. Comprehensive genomic profiling (CGP), a subtype of clinical next-generation sequencing (NGS), offers a uniquely comprehensive and convenient approach to detect the ever-increasing and "druggable" receptor-kinase rearrangements being discovered in lung cancer.</p> </sec> <sec> <title id="sect0015">Materials and methods</title> <p id="spar0010">We identified a novel <italic>ROS1</italic> fusion variant (<italic>TMEM106B-ROS1</italic>) in a stage IV adenocarcinoma of the lung never-smoker female patient during routine genomic profiling (FoundationOne<sup>®</sup>). This novel <italic>TMEM106B-ROS1</italic> fusion variant is generated by the fusion of exons 1–3 of <italic>TMEMB106B</italic> on chromosome 7p21 to the exons 35–43 of <italic>ROS1</italic> on chromosome 6q22. The predicted TMEM106-ROS1 protein product contains 540 amino acids comprising of the N-terminal amino acids 1–73 of TMEMB106 and C-terminal amino acids of 1881–2341 of ROS1. Although there is no predicted "coiled-coil" domain in the N-terminal domain of TMEM106B, the N-terminal domain of TMEM106B is involved in homo- and hetero-dimerization with other TMEM106 family members.</p> </sec> <sec> <title id="sect0020">Conclusions</title> <p id="spar0015"> <italic>TMEM106B-ROS1</italic> is a novel <italic>ROS1</italic> fusion variant in NSCLC identified by comprehensive genomic profiling and should be included in any <italic>ROS1</italic> detecting assay that depends on identifying the corresponding fusion partners such as reverse transcriptase-polymerase chain reaction (RT-PCR).</p> </sec> </abstract>