Clinicopathologic and molecular analysis of a BCOR–CCNB3 undifferentiated sarcoma of the kidney reveals significant epigenetic alterations
- Tamara J. Hagoel1,2,9,
- Eduardo Cortes Gomez3,9,
- Ajay Gupta1,2,
- Clare J. Twist1,2,
- Rafal Kozielski4,
- Jeffrey C. Martin5,
- Lingui Gao5,
- Joseph Kuechle6,
- Prashant K. Singh7,
- Miranda Lynch8,
- Lei Wei8,
- Song Liu3,
- Jianmin Wang3 and
- Joyce E. Ohm5
- 1Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York 14203, USA;
- 2Department of Pediatric Hematology-Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14203, USA;
- 3Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14203, USA;
- 4Department of Pathology, Oishei Children's Hospital, Buffalo, New York 14203, USA;
- 5Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14203, USA;
- 6Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14203, USA;
- 7Center for Personalized Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14203, USA;
- 8Hauptman-Woodward Structural Institute, Buffalo, New York 14203, USA
- Corresponding author: joyce.ohm{at}roswellpark.org
-
↵9 These authors contributed equally to this work.
Abstract
Undifferentiated soft tissue sarcomas (UDSTSs) are a group of mesenchymal tumors that remain a diagnostic challenge because of their morphologic heterogeneity and unclear histologic origin (Peters et al., Mod Pathol 28: 575 [2015]). In this case report, we present the first multiomics molecular signature for a BCOR–CCNB3 sarcoma (BCS) that includes mutation analysis, gene expression, DNA methylation, and micro RNA (miRNA) expression. We identify a paucity of additional mutations in this tumor and detail that there is significant dysregulation of gene expression of epigenetic remodeling agents including key members of the PRC, Sin3A/3b, NuRD, and NcoR/SMRT complexes and the DNA methyltransferases DNMT1, DNMT3a, and DNMT3b. This is accompanied by significant DNA methylation changes and dysregulation of multiple miRNAs with known links to tumorigenesis. This study significantly increases our understanding of the BCOR effects on fusion-positive undifferentiated sarcomas at both the genomic and epigenomic level and suggests that as better-tailored and more refined treatment algorithms continue to evolve, epigenetic modifying agents should be further evaluated for their efficacy against these tumors.
Footnotes
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[Supplemental material is available for this article.]
- Received August 17, 2021.
- Accepted November 10, 2021.
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