Next generation sequencing of extraskeletal myxoid chondrosarcoma

// Elizabeth J. Davis 1 , Yi-Mi Wu 2 , Dan Robinson 2 , Scott M. Schuetze 1 , Laurence H. Baker 1 , Jyoti Athanikar 2 , Xuhong Cao 2 , Lakshmi P. Kunju 2 , Arul M. Chinnaiyan 2 , Rashmi Chugh 1 1 Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA 2 Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA Correspondence to: Rashmi Chugh, email: rashmim@umich.edu Keywords: extraskeletal myxoid chondrosarcoma, next generation sequencing, EWSR1-NR4A3 Received: July 29, 2016 Accepted: January 09, 2017 Published: February 21, 2017 ABSTRACT Extraskeletal myxoid chondrosarcoma (EMC) is an indolent translocation-associated soft tissue sarcoma with a high propensity for metastases. Using a clinical sequencing approach, we genomically profiled patients with metastatic EMC to elucidate the molecular biology and identify potentially actionable mutations. We also evaluated potential predictive factors of benefit to sunitinib, a multi-targeted tyrosine kinase inhibitor with reported activity in a subset of EMC patients. Between January 31, 2012 and April 15, 2016, six patients with EMC participated in the clinical sequencing research study. High quality DNA and RNA was isolated and matched normal samples underwent comprehensive next generation sequencing (whole or OncoSeq capture exome of tumor and normal, tumor PolyA+ and capture transcriptome). The expression levels of sunitinib targeted-kinases were measured by transcriptome sequencing for KDR, PDGFRA/B, KIT, RET, FLT1, and FLT4 . The previously reported EWSR1-NR4A3 translocation was identified in all patient tumors; however, other recurring genomic abnormalities were not detected. RET expression was significantly greater in patients with EMC relative to other types of sarcomas except for liposarcoma (p