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Abstract：
Noonan syndrome (NS), an autosomal dominant disorder, is characterized by short stature, congenital heart defects, developmental delay, and facial dysmorphism. PTPN11 mutations are the most common cause of NS. PTPN11 encodes a non-receptor protein tyrosine phosphatase, SHP2. Hematopoietic malignancies and solid tumors are associated with NS. Among solid tumors, brain tumors have been described in children and young adults but remain rather rare. We report a 16-year-old boy with PTPN11-related NS who, at the age of 12, was incidentally found to have a left temporal lobe brain tumor and a cystic lesion in the right thalamus. He developed epilepsy 2 years later. The temporal tumor was surgically resected because of increasing crises and worsening radiological signs. Microscopy showed nodules with specific glioneuronal elements or glial nodules, leading to the diagnosis of dysembryoplastic neuroepithelial tumor (DNT). Immunohistochemistry revealed positive nuclear staining with Olig2 and pERK in small cells. SHP2 plays a key role in RAS/MAPK pathway signaling which controls several developmental cell processes and oncogenesis. An amino-acid substitution in the N-terminal SHP2 domain disrupts the self-locking conformation and leads to ERK activation. Glioneuronal tumors including DNTs and pilocytic astrocytomas have been described in NS. This report provides further support for the relation of DNTs with RASopathies and for the implication of RAS/MAPK pathways in sporadic low-grade glial tumors including DNTs. © 2017 Wiley Periodicals, Inc.
摘要：
努南综合征（NS），常染色体显性疾病,以身材矮小为特征，先天性心脏缺陷,发育迟缓,和面部畸形。PTPN11突变是NS的最常见原因。PTPN11编码一种非受体蛋白酪氨酸磷酸酶，SHP2。造血系统恶性肿瘤和实体瘤与NS相关。在实体瘤中，脑肿瘤已经在儿童和年轻人中描述过，但仍然相当罕见。我们报告了一个16岁的男孩，患有PTPN11相关的NS，12岁时，偶然发现左颞叶脑肿瘤和右丘脑囊性病变。两年后他患上了癫痫。由于危机增加和放射学体征恶化，颞叶肿瘤被手术切除。显微镜检查显示结节具有特定的神经胶质神经元元素或神经胶质结节，导致胚胎发育不良神经上皮肿瘤（DNT）的诊断。免疫组织化学显示小细胞中Olig2和pERK的阳性核染色。SHP2在RAS/MAPK通路信号传导中起关键作用，该信号传导控制多个发育细胞过程和肿瘤发生。N末端SHP2结构域中的氨基酸取代破坏了自锁构象并导致ERK活化。已经在NS中描述了包括DNTs和毛细胞星形细胞瘤的神经神经肿瘤。该报告为DNT与放射病的关系以及RAS/MAPK途径在包括DNT在内的散发性低度胶质肿瘤中的意义提供了进一步的支持。©2017Wiley期刊，Inc.
