Undifferentiated Sarcomas in Children Harbor Clinically Relevant Oncogenic Fusions and Gene Copy-Number Alterations: A Report from the Children's Oncology Group

Clin Cancer Res. 2018 Aug 15;24(16):3888-3897. doi: 10.1158/1078-0432.CCR-18-0672. Epub 2018 Apr 24.


Purpose: A comprehensive analysis of the genomics of undifferentiated sarcomas (UDS) is lacking. We analyzed copy-number alterations and fusion status in patients with UDS prospectively treated on Children's Oncology Group protocol ARST0332.Experimental Design: Copy-number alterations were assessed by OncoScan FFPE Express on 32 UDS. Whole-exome and transcriptome libraries from eight tumors with sufficient archived material were sequenced on HiSeq (2 × 100 bp). Targeted RNA-sequencing using Archer chemistry was performed on two additional cases.Results: Five-year overall survival for patients with UDS was 83% (95% CI, 69%-97%) with risk-adapted therapy (surgery, chemotherapy, and radiotherapy). Both focal and arm-level copy-number alterations were common including gain of 1q (8/32, 25%) and loss of 1p (7/32, 22%), both of which occurred more often in clinically defined high-risk tumors. Tumors with both loss of 1p and gain of 1q carried an especially poor prognosis with a 5-year event-free survival of 20%. GISTIC analysis identified recurrent amplification of FGF1 on 5q31.3 (q = 0.03) and loss of CDKN2A and CDKN2B on 9p21.3 (q = 0.07). Known oncogenic fusions were identified in eight of 10 cases analyzed by next-generation sequencing.Conclusions: Pediatric UDS generally has a good outcome with risk-adapted therapy. A high-risk subset of patients whose tumors have copy-number loss of 1p and gain of 1q was identified with only 20% survival. Oncogenic fusions are common in UDS, and next-generation sequencing should be considered for children with UDS to refine the diagnosis and identify potentially targetable drivers. Clin Cancer Res; 24(16); 3888-97. ©2018 AACR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / genetics
  • Cell Differentiation / genetics
  • Child
  • Child, Preschool
  • Chromosome Aberrations
  • Combined Modality Therapy
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA Copy Number Variations / genetics
  • Drug Therapy*
  • Female
  • Fibroblast Growth Factor 1 / genetics
  • Gene Dosage
  • Genetic Predisposition to Disease
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Oncogene Proteins, Fusion / genetics
  • Progression-Free Survival
  • Radiotherapy*
  • Sarcoma / classification
  • Sarcoma / genetics*
  • Sarcoma / pathology
  • Sarcoma / therapy*
  • Transcriptome / genetics
  • Whole Exome Sequencing
  • Young Adult


  • Biomarkers, Tumor
  • CDKN2A protein, human
  • CDKN2B protein, human
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • Oncogene Proteins, Fusion
  • Fibroblast Growth Factor 1