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// Sujana Movva 1, * , Wenhsiang Wen 2, * , Wangjuh Chen 2 , Sherri Z. Millis 2 , Zoran Gatalica 2 , Sandeep Reddy 2 , Margaret von Mehren 1 , Brian A. Van Tine 3 1 Fox Chase Cancer Center, Philadelphia, PA, USA 2 Caris Life Sciences, Phoenix, AZ, USA 3 Washington University in St. Louis, St. Louis, MO, USA * These authors have contributed equally to this work Correspondence to: Sujana Movva, e-mail: sujana.movva@fccc.edu Keywords: sarcoma, biomarkers, targeted therapies, DNA sequencing, protein expression Received: February 03, 2015 Accepted: March 07, 2015 Published: March 26, 2015 ABSTRACT Background: Drug development in sarcoma has been hampered by the rarity and heterogeneity of the disease and lack of predictive biomarkers to therapies. We assessed protein expression and gene alterations in a large number of bone and soft tissue sarcomas in order to categorize the molecular alterations, identify predictive biomarkers and discover new therapeutic targets. Methods: Data from sarcoma specimens profiled for protein expression, gene amplification/translocation and DNA sequencing was reviewed. Results: 2539 sarcoma specimens of 22 subtypes were included. TOPO2A was the most overexpressed protein at 52.8%. There was overexpression or loss of other sarcoma relevant proteins such as SPARC, PTEN and MGMT. Approximately 50% of the sarcomas expressed PD-L1 by IHC and presented with PD-1+ TILs, notably the LMS, chondrosarcomas, liposarcomas and UPS. Gene amplification/rearrangement of ALK, cMYC, HER2, PIK3CA, TOPO2A and cMET was relatively uncommon. EGFR gene amplification occurred at a rate of 16.9%. DNA sequencing of 47 genes identified mutations in 47% of the samples. The most commonly mutated genes were TP53 (26.3%) and BRCA2 (17.6%). Overexpression of TOPO2A was associated with TP53 mutation ( P = 0.0001). Conclusion: This data provides the landscape of alterations in sarcoma. Future clinical trials are needed to validate these targets.
Movva et al. (Thu,) studied this question.