Abstract：
Recurrent NCOA1/2/3 gene fusions emerged in uterine tumor resembling ovarian sex cord tumor (UTROSCT). More cases are required to consolidate these molecular alterations. In this study, the clinicopathological features and immunostaining profiles were reviewed in 18 UTROSCT. Fluorescence in situ hybridization for dual color break-apart probes of NCOA1, NCOA2, NCOA3, BCOR, YWHAE, PHF1 and JAZF1 were performed on 16 tumors. Eight cases were subjected to targeted next-generation sequencing to detect genomic alterations. We found that the tumors predominantly showed various sex-cord patterns without a recognizable endometrial stromal component. They exhibited a diverse immunohistochemical profile, frequently co-expressing sex cord (calretinin, inhibin, WT1, SF-1, and FOXL2), smooth muscle (SMA, desmin and caldesmon), epithelial (CK) and other markers (CD10 and IFITM1). Fourteen of 16 tumors (87.5%) showed NCOA1-3 gene rearranges, but none had BCOR, YWHAE, PHF1 and JAZF1 fusions. Five tumors contained 6 non-recurrent pathogenic (likely) mutations and one had gains in c-MYC. Our study supports frequent NCOA1-3 rearrangements in UTROSCT. Rare, non-recurrent mutations suggest that these gene rearrangements be potential drivers in tumorigenesis. Detection of gene rearrangements can contribute to the correct interpretation of UTROSCT. However, large comparative studies with molecular tests are required to confirm these findings.
摘要：
复发性NCOA1/2/3基因融合出现在类似于卵巢性索肿瘤（UTROSCT）的子宫肿瘤中。需要更多的病例来巩固这些分子改变。在这项研究中,在18个UTROSCT中回顾了临床病理特征和免疫染色谱。NCOA1、NCOA2、NCOA3、BCOR双色分离探针的荧光原位杂交,YWHAE,对16个肿瘤进行PHF1和JAZF1。对8例病例进行靶向下一代测序以检测基因组改变。我们发现肿瘤主要表现出各种性索模式，而没有可识别的子宫内膜基质成分。他们表现出不同的免疫组织化学特征，经常共表达性索(calretinin，抑制素,WT1、SF-1和FOXL2)，平滑肌（SMA，desmin和caldesmon)，上皮（CK）和其他标志物（CD10和IFITM1）。16例肿瘤中有14例（87.5%）显示NCOA1-3基因重排，但都没有BCOR,YWHAE,PHF1和JAZF1融合。五个肿瘤包含6个非复发性致病性（可能）突变，一个在c-MYC中增加。我们的研究支持UTROSCT中频繁的NCOA1-3重排。稀有,非复发突变提示这些基因重排是肿瘤发生的潜在驱动因素.基因重排的检测有助于UTROSCT的正确解释。然而,需要通过分子测试进行大型比较研究来证实这些发现。
