带有BCOR基因改变（BCOR相关肉瘤）的肉瘤是一类最近被认识出的软组织和骨肿瘤家族，其特征为BCOR融合、BCOR内串联重复或YWHAE::NUTM2B融合。在组织学上，肿瘤显示为可变血管化间质中的椭圆形-纺锤形细胞增殖，并过表达BCOR和SATB2。在本文中，我们描述了三种有KDM2B融合的软组织肉瘤，表型和表观遗传学方面与BCOR相关肉瘤相匹配。这些病例包括一个婴儿、一个青少年和一个年长患者。所有肿瘤的组织学发现与BCOR相关肉瘤无法区分，并且根据表型最初诊断为BCOR相关肉瘤。然而，这些肿瘤中没有BCOR或YWHAE基因改变。相反，目标RNA测序鉴定出了KDM2B::NUTM2B、KDM2B::CREBBP和KDM2B::DUX4等整合融合。通过逆转录-聚合酶链反应、Sanger测序和原位杂交测试验证了KDM2B融合。基因组范围的DNA甲基化分析使用DKFZ分类器和t-SNE分析将所有三个肿瘤与BCOR相关肉瘤相匹配。一个局部肿瘤显示出平坦的基因组范围拷贝数谱，患者在治疗后一直没有疾病复发。其他肿瘤显示出多个拷贝数改变，包括MDM2/CDK4扩增和/或CDKN2A/B缺失，并且两个肿瘤发生转移，其中一个患者死亡。在使用KDM2B免疫组织化学检测时，所有三个具有KDM2B重排的肉瘤显示出弥漫性强阳性染色，而所有13个具有BCOR基因改变的肉瘤也显示出弥漫性强或弱阳性染色。相比之下，在72个类似肿瘤中，只有一部分滑膜肉瘤显示局灶性或弥漫性弱阳性KDM2B表达。总之，我们的研究认为，KDM2B重排的软组织肉瘤属于BCOR相关肉瘤家族，并扩展了其分子谱。这可能与KDM2B与BCOR在聚缩抑制复合物1.1中已知的分子关系有关。对KDM2B的免疫组织化学分析是诊断BCOR相关肉瘤的一种潜在有价值的工具，包括那些具有KDM2B重排的肉瘤。Copyright © 2023. Published by Elsevier Inc.

Sarcomas with BCOR genetic alterations (BCOR-associated sarcomas) represent a recently recognized family of soft tissue and bone tumors characterized by BCOR fusion, BCOR internal tandem duplication, or YWHAE::NUTM2B fusion. Histologically, the tumors demonstrate oval-spindle cell proliferation in a variably vascular stroma and overexpression of BCOR and SATB2. Herein, we describe three soft tissue sarcomas with KDM2B fusions that phenotypically and epigenetically match BCOR-associated sarcomas. The cases included one infant, one adolescent, and one older patient. All tumors showed histological findings indistinguishable from those of BCOR-associated sarcomas and were originally diagnosed as such based on the phenotype. However, none of the tumors had BCOR or YWHAE genetic alterations. Instead, targeted RNA sequencing identified in-frame KDM2B::NUTM2B, KDM2B::CREBBP, and KDM2B::DUX4 fusions. KDM2B fusions were validated using reverse transcription-polymerase chain reaction, Sanger sequencing, and in situ hybridization assays. Genome-wide DNA methylation analysis matched all three tumors with BCOR-associated sarcomas using the DKFZ classifier and t-SNE analysis. One localized tumor showed a flat genome-wide copy number profile, and the patient remained disease-free after treatment. The other tumors showed multiple copy number alterations, including MDM2/CDK4 amplification and/or CDKN2A/B loss, and both tumors metastasized, leading to the patient's death in one of the cases. When tested using KDM2B immunohistochemistry, all three KDM2B-rearranged sarcomas showed diffuse strong staining, and all 13 sarcomas with BCOR genetic alterations also demonstrated diffuse, strong or weak staining. By contrast, among 72 mimicking tumors, only a subset of synovial sarcomas showed focal or diffuse weak KDM2B expression. In conclusion, our study suggests that KDM2B-rearranged soft tissue sarcomas belong to the BCOR-associated sarcoma family and expand its molecular spectrum. This may be related to the known molecular relationship between KDM2B and BCOR in the polycomb repressive complex 1.1. Immunohistochemical analysis of KDM2B is a potentially valuable diagnostic tool for BCOR-associated sarcomas, including those with KDM2B rearrangement.Copyright © 2023. Published by Elsevier Inc.