Multi-platform profiling of over 2000 sarcomas: Identification of biomarkers and novel therapeutic targets
| Autor: | Sandeep K. Reddy, Brian A. Van Tine, Wangjuh Chen, Margaret von Mehren, Zoran Gatalica, Sherri Z. Millis, Wenhsiang Wen, Sujana Movva |
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| Rok vydání: | 2015 |
| Předmět: |
sarcoma
biology biomarkers Chromosomal translocation Sequence Analysis DNA medicine.disease targeted therapies DNA sequencing Oncology Mutation Gene duplication Biomarkers Tumor biology.protein medicine Cancer research Humans PTEN Immunohistochemistry EGFR Gene Amplification Sarcoma protein expression Gene In Situ Hybridization Fluorescence Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.3498 |
| Popis: | // 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. |
| Databáze: | OpenAIRE |
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