Targeted next generation sequencing of well-differentiated/ dedifferentiated liposarcoma reveals novel gene amplifications and mutations

// Neeta Somaiah 1 , Hannah C Beird 2 , Andrea Barbo 3 , Juhee Song 3 , Kenna R. Mills Shaw 4 , Wei-Lien Wang 5 , Karina Eterovic 4 , Ken Chen 4 , Alexander Lazar 5 , Anthony P. Conley 1 , Vinod Ravi 1 , Patrick Hwu 6 , Andrew Futreal 2 , George Simon 8 , Funda Meric-Bernstam 7 and David Hong 7 1 Department of Sarcoma Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA 2 Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA 3 Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA 4 Khalifa Institute for Personalized Cancer Therapy (IPCT), University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA 5 Department of Pathology, University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA 6 Division Chair, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA 7 Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA 8 Department of Thoracic Medical Oncology, University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA Correspondence to: Neeta Somaiah, email: nsomaiah@mdanderson.org Keywords: well-differentiated and dedifferentiated liposarcoma sequencing; targeted therapy; MDM2 inhibitors Received: November 18, 2016      Accepted: February 20, 2018      Published: April 13, 2018 ABSTRACT Well-differentiated/dedifferentiated liposarcoma is a common soft tissue sarcoma with approximately 1500 new cases per year. Surgery is the mainstay of treatment but recurrences are frequent and systemic options are limited. ‘Tumor genotyping’ is becoming more common in clinical practice as it offers the hope of personalized targeted therapy. We wanted to evaluate the results and the clinical utility of available next-generation sequencing panels in WD/DD liposarcoma. Patients who had their tumor sequenced by either FoundationOne ( n = 13) or the institutional T200/T200.1 panels ( n = 7) were included in this study. Significant copy number alterations were identified, but mutations were infrequent. Out of the 27 mutations detected in 7 samples, 8 ( CTNNB1, MECOM, ZNF536, EGFR, EML4, CSMD3, PBRM1, PPP1R3A ) were identified as deleterious (on Condel, PolyPhen and SIFT) and a truncating mutation was found in NF2 . Of these, EGFR and NF2 are potential driver mutations and have not been reported previously in liposarcoma. MDM2 and CDK4 amplification was universally present in all the tested samples and multiple other recurrent genes with high amplification or high deletion were detected. Many of these targets are potentially actionable. Eight patients went on to receive an MDM2 inhibitor with a median time to progression of 23 months (95% CI: 10-83 months).