Molecular analysis of astrocytomas presenting after age 10 in individuals with NF1
Molecular analysis of astrocytomas presenting after age 10 in individuals with NF1
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DOI：
10.1212/wnl.61.10.1397
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发表时间：
2003-11-25
期刊：
影响因子：
9.9
通讯作者：
Perry, A
中科院分区：
文献类型：
--
作者：
Gutmann, DH;James, CD;Perry, A
背景：15%至20%的1型神经纤维瘤病(NF1)儿童发展为低级别星形细胞瘤。尽管脑瘤在患有NF1的青少年和成年人中不太常见，但最近的研究表明，NF1患者患星形细胞瘤的风险显著增加。目的：探讨NF1患者在出生后10年后发生星形细胞瘤的遗传学基础。方法：采用荧光原位杂交、杂合性缺失、免疫组织化学和直接测序等方法对10例NF1相关星形细胞瘤进行分子遗传学分析。结果：发病较晚的NF1相关星形细胞瘤，与组织学上相同的散发性星形细胞瘤不同，表现出NF1失活，支持与NF1直接相关，而不是偶然发生。此外，其中一些星形细胞瘤存在NF1纯合子缺失。此外，在高级别散发性星形细胞瘤中观察到的基因变化，包括TP53突变和CDKN2A/p16缺失，也可见于NF1相关的高级别星形细胞瘤。结论：神经纤维瘤病1型相关星形细胞瘤发生在10岁以上的患者中，在散发性高级别星形细胞瘤中观察到基因变化。患有1型神经纤维瘤病和生殖系NF1缺失的患者可能有发生迟发性星形细胞瘤的风险。
Background: Fifteen to 20% of children with neurofibromatosis type 1 (NF1) develop low-grade astrocytomas. Although brain tumors are less common in teenagers and adults with NF1, recent studies have suggested that patients with NF1 are at a significantly increased risk of developing astrocytomas. Objectives: To investigate the genetic basis for astrocytoma development in patients with NF1 beyond the first decade of life. Methods: The authors performed molecular genetic analyses of 10 NF1-associated astrocytomas representing all World Health Organization (WHO) malignancy grades using fluorescence in situ hybridization, loss of heterozygosity, immunohistochemistry, and direct sequencing. Results: Later-onset NF1-associated astrocytomas, unlike histologically identical sporadic astrocytomas, exhibit NF1 inactivation, supporting a direct association with NF1 rather than a chance occurrence. Furthermore, some of these astrocytomas have homozygous NF1 deletion. In addition, genetic changes observed in high-grade sporadic astrocytomas, including TP53 mutation and CDKN2A/p16 deletion, are also seen in NF1-associated high-grade astrocytomas. Conclusions: Neurofibromatosis type 1-associated astrocytomas occurring in patients older than 10 years exhibit genetic changes observed in sporadic high-grade astrocytomas. Patients with neurofibromatosis type 1 and germline NF1 deletions may be at risk for developing late-onset astrocytomas.