ROS1 fusions rarely overlap with other oncogenes in NSCLC, study finds

This article in the May 2017 issues of the Journal of Thoracic Oncology analyzed genomic profiles of two ROS1+ non-small cell lung cancer (NSCLC) patient groups: 62 patients at Massachusetts General Hospital, and 166 patients who had been sequenced by Foundation Medicine.  The ROS1+ cancer in these patients rarely tested positive for EGFR, KRAS, or other oncogenes (such as ALK, BRAF, or PIK3CA).

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ROS1 Fusions Rarely Overlap with Other Oncogenic Drivers in Non–Small Cell Lung Cancer

 

Abstract

INTRODUCTION: Chromosomal rearrangements involving the gene ROS1 define a distinct molecular subset of NSCLCs with sensitivity to ROS1 inhibitors. Recent reports have suggested a significant overlap between ROS1 fusions and other oncogenic driver alterations, including mutations in EGFR and KRAS.

METHODS: We identified patients at our institution with ROS1-rearranged NSCLC who had undergone testing for genetic alterations in additional oncogenes, including EGFR, KRAS, and anaplastic lymphoma receptor tyrosine kinase gene (ALK). Clinicopathologic features and genetic testing results were reviewed. We also examined a separate database of ROS1-rearranged NSCLCs identified through the commercial FoundationOne assay (Foundation Medicine, Cambridge, MA).

RESULTS: Among 62 patients with ROS1-rearranged NSCLC evaluated at our institution, none harbored concurrent ALK fusions (0%) or EGFR activating mutations (0%). KRAS mutations were detected in two cases (3.2%), one of which harbored a concurrent noncanonical KRAS I24N mutation of unknown biological significance. In a separate ROS1 fluorescence in situ hybridization-positive case, targeted sequencing failed to confirm a ROS1 fusion but instead identified a KRAS G13D mutation. No concurrent mutations in B-Raf proto-oncogene, serine/threonine kinase gene (BRAF), erb-b2 receptor tyrosine kinase 2 gene (ERBB2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA), AKT/serine threonine kinase 1 gene (AKT1), or mitogen-activated protein kinase kinase 1 gene (MAP2K1) were detected. Analysis of an independent data set of 166 ROS1-rearranged NSCLCs identified by FoundationOne demonstrated rare cases with co-occurring driver mutations in EGFR (one of 166) and KRAS (three of 166) and no cases with co-occurring ROS1 and ALK rearrangements.

CONCLUSIONSROS1 rearrangements rarely overlap with alterations in EGFR, KRAS, ALK, or other targetable oncogenes in NSCLC.

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Gray Connections

I was diagnosed with non-small cell lung cancer in May 2011. The cancer became metastatic in October 2011. No, I never smoked anything (except a salmon). I've had no evidence of disease since January 2013 thanks to precision medicine, clinical trials, and other patients. ANYONE can get lung cancer. Using my engineering degrees (MIT SBME 1978, Caltech Aeronautics MS 1984 and ENGR 1986), I enjoyed a 20-year career in aerospace systems engineering as a technical translator of sorts: I researched a scientific or engineering subject and helped others understand how this new gizmo could benefit them. In the time I have left, I want to use my skills to help others who have lung cancer, and increase the visibility and knowledge of lung cancer among those who don't. I also study brain research, enjoy traveling, write science fiction, and geek out about all sorts of science stuff.