Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York 14203, USA.
Department of Pediatric Hematology-Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14203, USA.
Cold Spring Harb Mol Case Stud. 2022 Jan 10;8(1). doi: 10.1101/mcs.a005942. Print 2022 Jan.
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., 575 [2015]). In this case report, we present the first multiomics molecular signature for a 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.
未分化软组织肉瘤(UDSTSs)是一组间叶肿瘤,由于其形态学异质性和不明的组织学起源,仍然是一个诊断挑战(Peters 等人,575 [2015])。在本病例报告中,我们首次提出了包括突变分析、基因表达、DNA 甲基化和 microRNA(miRNA)表达在内的肉瘤(BCS)的多组学分子特征。我们发现该肿瘤中缺乏额外的突变,并详细说明包括 PRC 关键成员、Sin3A/3b、NuRD 和 NcoR/SMRT 复合物以及 DNA 甲基转移酶 DNMT1、DNMT3a 和 DNMT3b 在内的表观遗传重塑剂的基因表达存在显著失调。这伴随着多个 miRNA 的显著 DNA 甲基化变化和失调,这些 miRNA 与肿瘤发生有已知联系。这项研究极大地增加了我们对 BCOR 在基因组和表观基因组水平上对融合阳性未分化肉瘤的影响的理解,并表明随着更好定制和更精细的治疗算法不断发展,应进一步评估表观遗传修饰剂对这些肿瘤的疗效。
Cold Spring Harb Mol Case Stud. 2022-1
Pathol Res Pract. 2017-11
J Pathol Transl Med. 2025-1
Bioinformatics. 2021-10-11
Epigenomics. 2019-5-31
BMC Bioinformatics. 2019-5-14
Nat Commun. 2019-3-4
BMC Cancer. 2019-1-8
Biomed Pharmacother. 2018-12-12
J Cell Physiol. 2018-9-26