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

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posted on 2023-03-31, 21:43 authored by Theodore W. Laetsch, Angshumoy Roy, Lin Xu, Jennifer O. Black, Cheryl M. Coffin, Yueh-Yun Chi, Jing Tian, Sheri L. Spunt, Douglas S. Hawkins, Julia A. Bridge, D. Williams Parsons, Stephen X. Skapek

Supplementary Figures 1 and 2 Supplementary Figure 1: Representative photomicrographs of the spindle cell (A), round cell (B), and epithelioid (C) variants of undifferentiated sarcoma Supplementary Figure 2: GISTIC analysis of recurrent focal copy number alterations

Funding

Children's Oncology Group

Cancer Prevention and Research Institute of Texas (CPRIT)

St. Baldrick's Foundation

Children's Cancer Fund

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ARTICLE ABSTRACT

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.

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