Research Papers:

Next generation sequencing of extraskeletal myxoid chondrosarcoma

Elizabeth J. Davis, Yi-Mi Wu, Dan Robinson, Scott M. Schuetze, Laurence H. Baker, Jyoti Athanikar, Xuhong Cao, Lakshmi P. Kunju, Arul M. Chinnaiyan and Rashmi Chugh _

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Oncotarget. 2017; 8:21770-21777. https://doi.org/10.18632/oncotarget.15568

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Elizabeth J. Davis1, Yi-Mi Wu2, Dan Robinson2, Scott M. Schuetze1, Laurence H. Baker1, Jyoti Athanikar2, Xuhong Cao2, Lakshmi P. Kunju2, Arul M. Chinnaiyan2, Rashmi Chugh1

1Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

2Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA

Correspondence to:

Rashmi Chugh, email: [email protected]

Keywords: extraskeletal myxoid chondrosarcoma, next generation sequencing, EWSR1-NR4A3

Received: July 29, 2016    Accepted: January 09, 2017    Published: February 21, 2017


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<0.0002). The folate receptor was overexpressed in two patients. Our study demonstrated that similar to other translocation-associated sarcomas, the mutational profile of metastatic EMC is limited beyond the pathognomonic translocation. The clinical significance of RET expression in EMC should be explored. Additional pre-clinical investigations of EMC may help elucidate molecular mechanisms contributing to EMC tumorigenesis that could be translated to the clinical setting.

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