Two cases of nevoid basal cell carcinoma syndrome associated with meningioma caused by a PTCH1 or SUFU germline mutation
Two cases of nevoid basal cell carcinoma syndrome associated with meningioma caused by a PTCH1 or SUFU germline mutation
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DOI：
10.1007/s10689-012-9548-0
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发表时间：
2012-12-01
期刊：
影响因子：
2.2
通讯作者：
Fujii, Kiyotaka
中科院分区：
文献类型：
--
作者：
Kijima, Chihiro;Miyashita, Toshiyuki;Fujii, Kiyotaka
痣样基底细胞癌综合征（NBCCS）是一种以发育缺陷和肿瘤发生为特征的常染色体显性遗传疾病。负责NBCCS的基因是PTCH 1。NBCCS患者发生脑膜瘤是一种罕见的事件。在这里，我们报告两例NBCCS中脑膜瘤的发展。第一个患者携带一个PTCH 1等位基因的种系突变，c.290dupA（p.N97KfsX43）。此外，脑膜瘤样本在同一基因的另一个等位基因中携带体细胞突变c.307delG（p.Val103LeufsX15），表明第二次命中。这是第一例用标准的两次打击假说解释的NBCCS相关脑膜瘤。第二例患者在SUFU基因中存在生殖系无义突变，c.550C > T（p.Q184X）。SUFU位于音速刺猬信号通路中PTCH 1的下游。这是第二次发现SUFU的生殖系突变导致NBCCS。连同先前的报告描述了3例非NBCCS髓母细胞瘤携带该基因的种系突变，预计具有SUFU种系突变的个体发生髓母细胞瘤和脑膜瘤的风险明显较高。
Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental defects and tumorigenesis. The gene responsible for NBCCS is PTCH1. The development of meningioma in NBCCS patients is a rare event. Here, we report two cases of NBCCS in which meningiomas did develop. The first patient carried a germline mutation in one allele of PTCH1, c.290dupA (p.N97KfsX43). In addition, the meningioma sample carried a somatic mutation, c.307delG (p.Val103LeufsX15), in the other allele of the same gene, suggesting a second hit. This is the first case of NBCCS-associated meningioma explained by the standard two-hit hypothesis. The second patient had a germline nonsense mutation in the SUFU gene, c.550C > T (p.Q184X). SUFU is located downstream of PTCH1 in the sonic hedgehog signaling pathway. This is the second time a germline mutation in SUFU has been found to cause NBCCS. Together with the previous report describing three cases of non-NBCCS medulloblastoma carrying a germline mutation in this gene, individuals with a SUFU germline mutation are expected to have a markedly high risk of developing medulloblastoma and probably meningioma.