WTX遗传变异在家族性髓母细胞瘤发生发展中的作用研究

髓母细胞瘤是儿童最常见的颅内肿瘤，早期无明显临床症状，手术切除配合术后放、化疗可以延长患儿生存期。关于髓母细胞瘤致病遗传学变异的研究迄今仍未见突破。本课题组收集到一个髓母细胞瘤多发家系，前期研究发现位于X染色体上的WTX基因变异与该病的发生密切相关。WTX已被证实是Wnt信号通路的负向调控因子，其变异是儿童肾母细胞瘤关键致病基因之一，但其突变在髓母细胞瘤中未见报导。本研究将以该家系为基础，深入探讨WTX基因变异在髓母细胞瘤发病过程中的重要作用，寻找与WTX相互作用的其他遗传变异，并在散发病例中进行验证，为完善髓母细胞瘤发病的分子遗传学特征提供依据。另外，我们还将针对这些遗传变异（1）与分子诊断科合作，寻找在散发人群中开展早期筛查、早期诊断的方法；（2）寻找干预靶点，争取延缓遗传变异携带者发病，给患者提供早诊早治的方案。本研究将为提高髓母细胞瘤早诊早治、改善患者预后提供科学依据。

Medulloblasotma is the most frequent children brain tumor, which with no significant clinical symptoms. Surgery with concurrent radio- and chemotherapy prolongs the over all survival of patients remarkably. The genetic background of medulloblastoma was studied widely for many years, but no dramatic progresses received. Our group recruited one familial medulloblastoma with two patients recently. Preliminary data shown that WTX gene, located in X-chromosome was highly suspected for the familial medulloblastoma WTX was reported a negative regulator of Wnt signaling pathway and the driver gene for the occur of Wilms tumor, but never related with medulloblastoma. In the current study we will further confirm the role of WTX alteration in the development of medulloblastoma, as well as the related gene variations interacted with WTX. The validation in the other family members and the sporadic medulloblastomas will give us the map how WTX as well other genes involves in the formation of the disease. Furthermore, we will focus on the gene alterations to 1), explore the methods for the early detection of candidate gene alterations in healthy people, 2), look for the potential intervention strategies to slow down the disease progress. We are trying to improve the early detection of medulloblastoma and the life quality of patients.