Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas
Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas
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DOI：
10.1158/0008-5472.can-04-1170
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发表时间：
2004-08-01
期刊：
影响因子：
11.2
通讯作者：
Yan, H
中科院分区：
文献类型：
--
作者：
Broderick, DK;Di, CH;Yan, H
磷脂酰肌醇3'-激酶途径在多种晚期癌症中被激活，包括胶质母细胞瘤，通过PTEN肿瘤抑制基因失活。最近，PIK3CA（磷脂酰肌醇3'-激酶催化亚基家族的一名成员）突变被发现存在于相当一部分（25-30%）的结直肠癌、胃癌和胶质母细胞瘤以及一小部分乳腺癌和肺癌中。这些突变被发现集中在位于螺旋结构域和催化结构域的两个主要“热点”。为了确定PIK3CA是否在脑肿瘤中发生基因改变，我们对其螺旋结构域和催化结构域进行了大规模的突变分析。在间变性少突胶质细胞瘤、间变性星形细胞瘤、多形性胶质母细胞瘤和髓母细胞瘤中，共有13个PIK3CA特异结构域突变被发现，而在室管膜瘤或低级别星形细胞瘤中，未发现突变。这些观察结果暗示PIK3CA在成人和儿童脑肿瘤的更广泛范围内是一种致癌基因，并提示PIK3CA可能是这些癌症的有用诊断标记或治疗靶点。
The phosphatidylinositol 3'-kinase pathway is activated in multiple advanced cancers, including glioblastomas, through inactivation of the PTEN tumor suppressor gene. Recently, mutations in PIK3CA, a member of the family of phosphatidylinositol 3'-kinase catalytic subunits, were identified in a significant fraction (25-30%) of colorectal cancers, gastric cancers, and glioblastomas and in a smaller fraction of breast and lung cancers. These mutations were found to cluster into two major "hot spots" located in the helical and catalytic domains. To determine whether PIK3CA is genetically altered in brain tumors, we performed a large-scale mutational analysis of the helical and catalytic domains. A total of 13 mutations of PIK3CA within these specific domains were identified in anaplastic oligodendrogliomas, anaplastic astrocytomas, glioblastoma multiforme, and medulloblastomas, whereas no mutations were identified in ependymomas or low-grade astrocytomas. These observations implicate PIK3CA as an oncogene in a wider spectrum of adult and pediatric brain tumors and suggest that PIK3CA may be a useful diagnostic marker or a therapeutic target in these cancers.