Oncotarget

Research Papers:

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

Neeta Somaiah _, Hannah C. Beird, Andrea Barbo, Juhee Song, Kenna R. Mills Shaw, Wei-Lien Wang, Karina Eterovic, Ken Chen, Alexander Lazar, Anthony P. Conley, Vinod Ravi, Patrick Hwu, Andrew Futreal, George Simon, Funda Meric-Bernstam and David Hong

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Oncotarget. 2018; 9:19891-19899. https://doi.org/10.18632/oncotarget.24924

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Abstract

Neeta Somaiah1, Hannah C Beird2, Andrea Barbo3, Juhee Song3, Kenna R. Mills Shaw4, Wei-Lien Wang5, Karina Eterovic4, Ken Chen4, Alexander Lazar5, Anthony P. Conley1, Vinod Ravi1, Patrick Hwu6, Andrew Futreal2, George Simon8, Funda Meric-Bernstam7 and David Hong7

1Department of Sarcoma Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA

2Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA

3Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA

4Khalifa Institute for Personalized Cancer Therapy (IPCT), University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA

5Department of Pathology, University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA

6Division Chair, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA

7Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA

8Department of Thoracic Medical Oncology, University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA

Correspondence to:

Neeta Somaiah, email: [email protected]

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).


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