title: Multi-platform profiling of over 2000 sarcomas: identification of biomarkers and novel therapeutic targets.
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).
  
  
  CONCLUSIONS
  This data provides the landscape of alterations in sarcoma. Future clinical trials are needed to validate these targets.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Sujana
authors.initials: S
authors.lastname: Movva
authors.affiliation: Caris Life Sciences, Phoenix, AZ, USA.
authors.forename: Wenhsiang
authors.initials: W
authors.lastname: Wen
authors.affiliation: Caris Life Sciences, Phoenix, AZ, USA.
authors.forename: Wangjuh
authors.initials: W
authors.lastname: Chen
authors.affiliation: Caris Life Sciences, Phoenix, AZ, USA.
authors.forename: Sherri Z
authors.initials: SZ
authors.lastname: Millis
authors.affiliation: Caris Life Sciences, Phoenix, AZ, USA.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gatalica
authors.affiliation: Caris Life Sciences, Phoenix, AZ, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Reddy
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: von Mehren
authors.affiliation: Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Van Tine
mesh_terms: D014408:Biomarkers, Tumor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D009154:Mutation; D012509:Sarcoma / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D014408:Biomarkers, Tumor
keywords: DNA sequencing; biomarkers; protein expression; sarcoma; targeted therapies