Germline mutations in shelterin complex genes are associated with familial glioma.
Germline mutations in shelterin complex genes are associated with familial glioma.
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DOI：
10.1093/jnci/dju384
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发表时间：
2015-01-01
期刊：
影响因子：
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通讯作者：
Bondy, Melissa L
中科院分区：
文献类型：
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作者：
Bainbridge, Matthew N;Armstrong, Georgina N;Bondy, Melissa L
胶质瘤是最常见的脑肿瘤，具有不同恶性等级的几种组织学亚型。家族性胶质瘤的遗传贡献还不清楚。使用来自55个家庭的90个个体的全外显子组测序，我们确定了两个POT1突变的家庭（p.G95C，p.E450X），POT1是端粒掩蔽蛋白复合物的一个成员，每个家庭中的两个受影响的个体共享，并预测分别影响DNA结合和TPP1结合。在来自246个家庭的264名个体的单独队列中进行的验证确定了POT1中的另一个突变（p.D617Efs），也预测会破坏TPP1结合。所有POT1突变的家族都有少突胶质细胞瘤的成员，少突胶质细胞瘤是一种对辐射更敏感的胶质细胞瘤亚型。这些发现对于了解胶质瘤的起源具有重要意义，并可能对未来胶质瘤的诊断和治疗具有重要意义。
Gliomas are the most common brain tumor, with several histological subtypes of various malignancy grade. The genetic contribution to familial glioma is not well understood. Using whole exome sequencing of 90 individuals from 55 families, we identified two families with mutations in POT1 (p.G95C, p.E450X), a member of the telomere shelterin complex, shared by both affected individuals in each family and predicted to impact DNA binding and TPP1 binding, respectively. Validation in a separate cohort of 264 individuals from 246 families identified an additional mutation in POT1 (p.D617Efs), also predicted to disrupt TPP1 binding. All families with POT1 mutations had affected members with oligodendroglioma, a specific subtype of glioma more sensitive to irradiation. These findings are important for understanding the origin of glioma and could have importance for the future diagnostics and treatment of glioma.