Mutesa Léon, Pierquin Geneviève, Janin Nicolas, Segers Karin, Thomée Caroline, Provenzi Massimo, Bours Vincent
Center for Human Genetics, University Hospital Center-CHU Sart-Tilman, University of Liège, 4000 Liège, Belgium.
Cancer Genet Cytogenet. 2008 Apr 1;182(1):40-2. doi: 10.1016/j.cancergencyto.2007.12.005.
Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, typical craniofacial dysmorphism, skeletal anomalies, congenital heart defects, and predisposition to malignant tumors. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene. To date, solid tumors, and particularly brain tumors and rhabdomyosarcomas, have been documented in patients with NS; however, few cases of neuroblastoma associated with NS have been reported. Here we report an unusual case of neuroblastoma with mediastinal, retroperitoneal, and medullar locations associated in a NS patient carrying a PTPN11 germline missense mutation (p.G60A). This missense mutation occurs within the N-SH2 domain of the PTPN11 gene and has been reported to be associated with acute leukemia in NS patients. The association of this p.G60A PTPN11 mutation with neuroblastoma provides new evidence that gain of function PTPN11 mutations may play an important role in the pathogenesis of solid tumors associated with Noonan syndrome.
努南综合征（NS）是一种常染色体显性疾病，其特征为身材矮小、典型的颅面部畸形、骨骼异常、先天性心脏缺陷以及易患恶性肿瘤。在大约50%的病例中，该疾病由PTPN11基因的错义突变引起。迄今为止，已记录到NS患者患有实体瘤，尤其是脑肿瘤和横纹肌肉瘤；然而，与NS相关的神经母细胞瘤病例报告较少。在此，我们报告一例不寻常的神经母细胞瘤病例，该病例发生在一名携带PTPN11种系错义突变（p.G60A）的NS患者身上，并伴有纵隔、腹膜后和髓质部位病变。这种错义突变发生在PTPN11基因的N-SH2结构域内，据报道与NS患者的急性白血病有关。这种p.G60A PTPN11突变与神经母细胞瘤的关联提供了新的证据表明，功能获得性PTPN11突变可能在与努南综合征相关的实体瘤发病机制中起重要作用。
