ROS1-GOPC/FIG : a novel gene fusion in hepatic angiosarcoma

// Eric I. Marks 1, * , Sahithi Pamarthy 2, * , Don Dizon 1 , Ari Birnbaum 1 , Evgeny Yakirevich 3 , Howard Safran 1 and Benedito A. Carneiro 1 1 Division of Hematology-Oncology, Lifespan Cancer Institute, Warren-Alpert Medical School of Brown University, Providence, RI, USA 2 Atrin Pharmaceuticals, Pennsylvania Biotechnology Center, Doylestown, PA, USA 3 Department of Pathology, Lifespan Cancer Institute, Warren-Alpert Medical School of Brown University, Providence, RI, USA * These authors contributed equally to this work Correspondence to: Benedito A. Carneiro, email: Benedito.carneiro@lifespan.org Keywords: ROS1; GOPC; FIG; angiosarcoma; Targeted Therapy Received: October 22, 2018      Accepted: December 12, 2018      Published: January 04, 2019 ABSTRACT Hepatic angiosarcoma (HAS) is a rare and highly lethal malignancy with few effective systemic treatments. Relatively little is known about the genetic abnormalities that drive this disease. As a result, there has been minimal progress towards applying targeted therapies to the treatment of HAS. We describe the first reported case of a patient with HAS that harbored a fusion of ROS1 with GOPC/FIG . Similar to other rearrangements involving ROS1 , the resulting fusion protein is believed to act as a major driver of carcinogenesis and may be subject to inhibition by drugs that target ROS1 such as crizotinib. We then queried the MSK-IMPACT clinical sequencing cohort and cBioportal datasets, demonstrating the previously unknown prevalence of ROS1-GOPC fusions in soft tissue sarcomas and hepatobiliary cancers. Amplification of these genes was also found to correlate with reduced overall survival. This is followed by a review of the role played by ROS1 rearrangements in cancer, as well as the evidence supporting the use of targeted therapies against the resulting fusion protein. We suggest that testing for ROS1 fusion and, if positive, treatment with a targeted therapy could be considered at the time of diagnosis for patients with angiosarcoma. This report also highlights the need for further investigation into the molecular pathophysiology of this deadly disease.