Dramatic response to entrectinib in a patient with malignant peripheral nerve sheath tumor harboring novel SNRNP70-NTRK3 fusion gene
Dramatic response to entrectinib in a patient with malignant peripheral nerve sheath tumor harboring novel SNRNP70-NTRK3 fusion gene
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携带新型 SNRNP70-NTRK3 融合基因的恶性周围神经鞘瘤患者对恩曲替尼的显着反应
DOI：
10.1002/gcc.23089
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Tanaka S.
中科院分区：
文献类型：
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作者：
Kobayashi H;Makise N;Shinozaki-Ushiku A;Zhang L;Ishibashi Y;Ikegami M;Tsuda Y;Kohsaka S;Ushiku T;Oda K;Miyagawa K;Aburatani H;Mano H;Tanaka S.
原肌球蛋白受体激酶(NTRK)基因重排在少数肉瘤中已有报道，但迄今为止，在恶性周围神经鞘瘤(MPNSTs)中只有一例报道。在此，我们描述一位51岁男性患者，臀部肿瘤起源于坐骨神经，经免疫组织化学证实为MPNST，S-100染色阳性，SOX10染色阴性，组蛋白H3(H3K27me3)27位赖氨酸三甲基化缺失。原发肿瘤切除后不久，患者被发现有肺和淋巴转移。灯盏花素和曲贝替丁联合化疗效果有限。然而，患者对帕佐帕尼的反应很快，但严重的副作用导致停止治疗。RNA板检测发现小核糖核蛋白U1亚基70(SNRNP70)基因与NTRK3基因之间存在新的融合基因。此外，DNA板检测证实NF1、SUZ12和CDKN2A基因缺失，这与MPNST的组织学诊断相一致。SNRNP70具有卷曲结构域，似乎通过二聚作用诱导NTRK3的结构性激活。事实上，免疫组织化学显示PAN-TRK在肿瘤细胞内呈弥漫性染色。NTRK抑制剂entrectinib的治疗显示出10个月的快速和持久的反应。尽管NTRK重排在MPNST中非常罕见，但该病例突出了MPNST中基因检测的重要性，特别是使用RNA面板检测罕见的融合基因。
Neurotropic tropomyosin receptor kinase (NTRK) gene rearrangements have been reported in limited cases of sarcomas; however, to date, there has been only one report of such rearrangements in malignant peripheral nerve sheath tumors (MPNSTs). Herein, we describe a 51‐year‐old male patient with a buttock tumor arising from the sciatic nerve, which was diagnosed as MPNST with positive S‐100 staining, negative SOX10 staining, and loss of trimethylation at lysine 27 of histone H3 (H3K27me3) confirmed by immunohistochemistry. Soon after the resection of the primary tumor, the patient was found to have pulmonary and lymph node metastases. Chemotherapy with eribulin and trabectedin showed limited effects. However, the patient responded rapidly to pazopanib, but severe side effects caused discontinuation of the treatment. RNA panel testing revealed a novel fusion gene between Small Nuclear Ribonucleoprotein U1 Subunit 70 (SNRNP70)gene andNTRK3gene. Furthermore, loss ofNF1, SUZ12,andCDKN2Agenes was confirmed by DNA panel testing, which is compatible with a histological diagnosis of MPNST. SNRNP70 possesses a coiled‐coiled domain and seems to induce constitutive activation ofNTRK3through dimerization. In fact, immunohistochemistry revealed diffuse staining of pan‐TRK within tumor cells. Treatment with entrectinib, which is an NTRK inhibitor, showed a quick and durable response for 10 months. AlthoughNTRKrearrangements are very rare in MPNST, this case highlights the importance of genetic testing in MPNST, especially using an RNA panel for the detection of rare fusion genes.