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Multi-platform profiling of over 2000 sarcomas: Identification of biomarkers and novel therapeutic targets
Oncotarget. 2015 May 20;6(14) :12234-47
PMID: 25906748 PMCID: PMC4494935 URL: http://www.ncbi.nlm.nih.gov/pubmed/25906748
AbstractBACKGROUND: 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.
NotesMovva, Sujana Wen, Wenhsiang Chen, Wangjuh Millis, Sherri Z Gatalica, Zoran Reddy, Sandeep von Mehren, Margaret Van Tine, Brian A Oncotarget. 2015 Mar 26.