Novel GATA6-FOXO1 fusions in a subset of epithelioid hemangioma.
Novel GATA6-FOXO1 fusions in a subset of epithelioid hemangioma.
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DOI：
10.1038/s41379-020-00723-4
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Mechtersheimer G
中科院分区：
文献类型：
--
作者：
Antonescu CR;Huang SC;Sung YS;Zhang L;Helmke BM;Kirchner M;Stenzinger A;Mechtersheimer G
上皮样血管瘤（EH）的遗传标志是存在涉及FOS和FOSB转录因子的复发性基因融合，发生在三分之一的病例中。某些临床、病理和基因型相关性已经被描述，与FOSB相关的融合更常在EH的骨骼和细胞变异中检测到，而FOSB基因重排更常与非典型组织学特征和阴茎位置相关。这些融合很少在皮肤或头颈部EH中发现。总的来说，三分之二的EH缺乏这些典型融合，并且仍然难以分类，特别是当伴有非典型特征和/或临床表现时。通过靶向RNA测序（Archer®FusionPlex®Sarcoma Panel），我们研究了27例新的FOS和FOSB基因重排阴性的血管内软组织EH病例，以确定其复发潜力及其与临床和病理特征的关系。另外4例EH病例显示gata6 - fox01融合（18%）。女性3例，男性2例，平均年龄32岁。头颈部（硬脑膜、鼻咽部、脸颊）出现3个病变，背部1个，腿部1个。其中两个病变是皮肤的，一个是腿皮下的血管内病变。显微镜下，肿瘤形态多样，血管形成成分和实体成分交替存在，红细胞外渗，细胞异型性轻至中度。没有一例显示有丝分裂活跃或坏死。肿瘤免疫组化FOS和FOSB均为阴性。总之，我们报告了一种新的GATA6-FOXO1融合在EH的一个子集中，偏爱皮肤和头颈部。这种新的分子亚群与更常见的FOS/ fosb融合阳性EH的关系仍有待确定。
The genetic hallmark of epithelioid hemangioma (EH) is the presence of recurrent gene fusions involving FOS and FOSB transcription factors, which occur in one third of the cases. Certain clinical, pathologic and genotypic correlations have been described, with FOS-related fusions being more often detected in skeletal and cellular variants of EH, while FOSB gene rearrangements are more commonly associated with atypical histologic features and penile location. These fusions are infrequently detected in the cutaneous or head and neck EH. Overall, two-thirds of EH lack these canonical fusions and remain difficult to classify, especially when associated with atypical features and/or clinical presentations. Triggered by an index case of an intravascular soft tissue EH with a novel GATA6-FOXO1 gene fusion by targeted RNA sequencing (Archer® FusionPlex® Sarcoma Panel), we have investigated 27 additional EH cases negative for FOS and FOSB gene rearrangements for this novel abnormality to determine its recurrent potential and its association with clinical and pathologic features. Four additional EH cases were found to display GATA6-FOXO1 fusions (18 %). There were 3 females and 2 males, with a mean age of 32 years old. Three lesions occurred in the head and neck (dura, nasopharyngeal, cheek), one in the back and one in the leg. Two of these lesions were cutaneous and one was intravascular in the subcutis of the leg. Microscopically, the tumors showed a variegated morphology, with alternating vasoformative and solid components, extravasated red blood cells and mild to moderate cytologic atypia. None showed brisk mitotic activity or necrosis. Tumors were negative for FOS and FOSB by immunohistochemistry. In conclusion, we report a new GATA6-FOXO1 fusion in a subset of EH, with a predilection for skin and head and neck location. The relationship of this novel molecular subset with the more common FOS/FOSB-fusion positive EH remains to be determined.
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DOI：
10.1038/s41379-020-0505-4
发表时间：
2020-08
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
影响因子：
--
作者：
Luzar B;Ieremia E;Antonescu CR;Zhang L;Calonje E
通讯作者：
Calonje E
影响因子：
14.9
作者：
Hu X;Wang Q;Tang M;Barthel F;Amin S;Yoshihara K;Lang FM;Martinez-Ledesma E;Lee SH;Zheng S;Verhaak RGW
通讯作者：
Verhaak RGW
影响因子：
7.5
作者：
Antonescu, Cristina
通讯作者：
Antonescu, Cristina
影响因子：
3.7
作者：
Antonescu, Cristina R.;Chen, Hsiao-Wei;Fletcher, Christopher D.
通讯作者：
Fletcher, Christopher D.
影响因子：
5.6
作者：
Amary, Fernanda;Markert, Eva;Flanagan, Adrienne M.
通讯作者：
Flanagan, Adrienne M.