Data from Identifying and Targeting <i>ROS1</i> Gene Fusions in Non–Small Cell Lung Cancer

• DOI: 10.1158/1078-0432.c.6522059.v1
• Publication Date: 2023-04-01T06:50:02Z
• Authors: Kurtis D. Davies; Anh T. Le; Mariana F. Theodoro; Margaret C. Skokan; Dara L. Aisner; Eamon M. Berge; Luigi M. Terracciano; Federico Cappuzzo; Matteo Incarbone; Massimo Roncalli; Marco Alloisio; Armando Santoro; D. Ross Camidge; Marileila Varella...; Robert C. Doebele

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Oncogenic gene fusions involving the 3′ region of &lt;i&gt;ROS1&lt;/i&gt; kinase have been identified in various human cancers. In this study, we sought to characterize fusion genes non–small cell lung cancer (NSCLC) and establish proteins as drug targets.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; An NSCLC tissue microarray (TMA) panel containing 447 samples was screened for rearrangement by FISH. This assay also used screen patients with NSCLC. positive samples, identity partner determined through inverse PCR reverse transcriptase PCR. addition, clinical efficacy ROS1 inhibition assessed treating a ROS1-positive patient crizotinib. The HCC78 line, which expresses &lt;i&gt;SLC34A2–ROS1&lt;/i&gt; fusion, treated inhibitors that activity against ROS1. effects on proliferation, cell-cycle progression, signaling pathways were analyzed MTS assay, flow cytometry, Western blotting.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; TMA panel, 5 428 (1.2%) evaluable found be rearrangement. 1 48 tested rearrangement, showed tumor shrinkage upon treatment one sample displayed expression recently &lt;i&gt;SDC4–ROS1&lt;/i&gt; whereas two expressed &lt;i&gt;CD74–ROS1&lt;/i&gt; others fusion. cells, antiproliferative downregulated are critical growth survival.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; may an effective strategy subset whose tumors express genes. &lt;i&gt;Clin Cancer Res; 18(17); 4570–9. ©2012 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;