Central nervous system sarcoma with ATXN1::DUX4 fusion expands the concept of CIC-rearranged sarcoma
Central nervous system sarcoma with ATXN1::DUX4 fusion expands the concept of CIC-rearranged sarcoma
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ATXN1::DUX4 融合的中枢神经系统肉瘤扩展了 CIC 重排肉瘤的概念
DOI：
10.1002/gcc.23080
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Yoshida Akihiko
中科院分区：
文献类型：
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作者：
Satomi Kaishi;Ohno Makoto;Kubo Takashi;Honda‐Kitahara Mai;Matsushita Yuko;Ichimura Koichi;Narita Yoshitaka;Ichikawa Hitoshi;Yoshida Akihiko
CIC重排肉瘤是一种高度恶性的肉瘤，最常见的是CIC：：DUX4融合，其特征是具有独特的圆形细胞组织学，ETV4和WT1共表达，以及特定的DNA甲基化类别。在这里，我们报告了一个带有ATXN1：：DUX4的脑瘤，其表型和DNA甲基化特征与CIC重排的肉瘤没有区别。患者男，40岁，大脑右额叶有一个5厘米的出血性肿块。肿瘤被切除，组织学显示相对单一的圆形细胞密集增殖，伴有多灶性粘液样改变。免疫组织化学显示肿瘤广泛表达ETV4、WT1和DUX4。根据经典的组织形态和免疫图谱，肿瘤被暂时诊断为CIC重排肉瘤。然而，使用CIC分离荧光原位杂交(FISH)或FoundationOne CDX鉴定了非CIC融合或突变。尽管进行了多次手术和辅助放化疗，患者还是在出现16个月后死亡( )。RNA外显子测序检测到框内ATXN1(外显子9)：：DUX4(外显子1)融合，经逆转录-聚合酶链式反应和ATXN1FISH检测证实。在DNA甲基化分析中，肿瘤与CIC重排肉瘤通过Deutsche Krebsforschungszentum分类器和t分布随机邻近嵌入法进行匹配。结合最近一例类似的儿童脑瘤的报道，本病例表明ATXN1：：DUX4是肉瘤类型中的一种反复发生的替代分子事件，目前由CICreranging定义，这促使肿瘤概念的扩展。
CIC‐rearranged sarcoma is a high‐grade sarcoma, most often harboringCIC::DUX4fusion, and is characterized by a distinct round cell histology, co‐expression of ETV4 and WT1, and a specific DNA methylation class. Herein, we report a brain tumor withATXN1::DUX4that had an indistinguishable phenotype and DNA methylation profile fromCIC‐rearranged sarcoma. A 40‐year‐old man presented with a 5 cm hemorrhagic mass in the right frontal lobe of the cerebrum. The tumor was resected and histologically showed a dense proliferation of relatively monomorphic round cells with multifocal myxoid changes. Immunohistochemically, the tumor was diffusely positive for ETV4, WT1, and DUX4. Through classic histomorphology and immunoprofile, the tumor was provisionally diagnosed asCIC‐rearranged sarcoma. However, noCICfusions or mutations were identified usingCICbreak‐apart fluorescence in situ hybridization (FISH) or FoundationOne CDx. Despite multiple surgeries and adjuvant chemoradiation therapy, the patient succumbed 16 months after presentation. RNA exome sequencing detected an in‐frame intraexonicATXN1(exon 9)::DUX4(exon 1) fusion, which was validated by reverse transcription‐polymerase chain reaction andATXN1FISH assay. Upon DNA methylation analysis, the tumor matched withCIC‐rearranged sarcoma both by the Deutsche Krebsforschungszentrum classifier and t‐distributed stochastic neighbor embedding. Along with a recent report of a similar pediatric brain tumor, the present case suggests thatATXN1::DUX4is a recurrent alternative molecular event in the sarcoma type that is presently defined byCICrearrangement, which prompts an expansion of the tumor concept.