Novel PPP1CB-ALK fusion protein in a high-grade glioma of infancy.
Novel PPP1CB-ALK fusion protein in a high-grade glioma of infancy.
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DOI：
10.1136/bcr-2016-217189
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发表时间：
2016-08-16
期刊：
影响因子：
0.9
通讯作者：
Crawford, John Ross
中科院分区：
文献类型：
--
作者：
Aghajan, Yasmin;Levy, Michael L;Crawford, John Ross
一名原本健康的 3 个月大女孩因突然出现精神状态改变和心肺骤停而入院。她的右瞳孔固定并散大。紧急 CT 扫描显示，右侧大脑半球有一个 10.2 厘米的巨大高密度病变，并伴有急性出血区域，导致大脑镰下、钩回和小脑下疝，伴有梗阻性脑积水和弥漫性脑水肿（图 1）。在没有术前 MRI 的情况下，进行了紧急开颅手术以清除血肿并彻底切除肿块。神经病理学显示恶性胶质瘤具有显着的内皮增殖（图 2）。肿瘤的分子分析证明了一种新型 PPP1CB-ALK 融合蛋白。考虑到患者年龄较小且已完全切除，决定不再进行化疗。诊断后 3 年，该儿童仍无疾病，但存在明显的运动和神经认知迟缓。间变性淋巴瘤激酶（ALK）是一种首先在间变性大细胞淋巴瘤中发现的受体酪氨酸激酶。 1 ALK 融合蛋白具有致癌性，因为它们会激活细胞内信号级联，例如 Ras-ERK、JAK3-STAT3 和 PI3K-Akt 通路，1 和 PPP1CB（一种丝氨酸/苏氨酸磷酸酶）与这些通路的激活有关。 2 EML4-ALK 易位是实体癌中更常见的 ALK 突变，存在于 6% 的非小细胞肺癌中。 1 然而，ALK 融合蛋白传统上并未涉及原发性中枢神经系统实体瘤，这使得这种婴儿期高级神经胶质瘤成为罕见且独特的病例。总之，我们的研究结果揭示了原发性 CNS 肿瘤中的第一个 PPP1CB-ALK 融合蛋白突变。
A 3-month-old previously healthy girl presented to the hospital with sudden onset altered mental status and cardiopulmonary arrest. Her right pupil was fixed and dilated. Emergent CT scan showed a massive 10.2 cm hyperdense lesion occupying the right cerebral hemisphere with areas of acute haemorrhage causing subfalcine, uncal and inferior cerebellar herniation with obstructive hydrocephalus and diffuse cerebral oedema (figure 1). Emergent craniotomy was performed for evacuation of the haematoma and gross total resection of the mass in the absence of preoperative MRI. Neuropathology revealed a malignant glial tumour with prominent endothelial proliferation (figure 2). Molecular analysis of the tumour demonstrated a novel PPP1CB-ALK fusion protein. Given the patient’s young age and gross total resection, the decision was made not to proceed with chemotherapy. The child remains disease-free at 3years postdiagnosis with significant motor and neurocognitive delays. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase first discovered in anaplastic large cell lymphomas. 1 ALK fusion proteins are oncogenic, as they activate intracellular signalling cascades such as the Ras-ERK, JAK3-STAT3 and PI3K-Akt pathways, 1 and PPP1CB, a serine/threonine phosphatase, has been implicated in activating those pathways. 2 The EML4-ALK translocation is the more prevalent ALK mutation in solid cancers, present in 6% of non-small cell lung cancers. 1 However, ALK fusion proteins have not classically been implicated in primary CNS solid tumours, making this high-grade glioma of infancy a rare and unique case. In conclusion, our findings revealed the first PPP1CB-ALK fusion protein mutation in a primary CNS tumour.