Mutations in the human homologue of the Drosophila segment polarity gene patched (PTCH) in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system.
Mutations in the human homologue of the Drosophila segment polarity gene patched (PTCH) in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system.
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发表时间：
1997-07
期刊：
影响因子：
11.2
通讯作者：
M. Wolter;J. Reifenberger;C. Sommer;T. Ruzicka;G. Reifenberger
中科院分区：
文献类型：
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作者：
M. Wolter;J. Reifenberger;C. Sommer;T. Ruzicka;G. Reifenberger
果蝇体节极性基因patched（PTCH）的人类同源基因最近被鉴定为负责痣样基底细胞癌（BCC）综合征的肿瘤抑制基因（H。Hahn等人，Cell，85：841-851，1996; R. L.约翰逊等人，Science（华盛顿DC），272：1668-1671，1996）。除了多发性基底细胞癌外，痣样基底细胞癌综合征患者还易发生中枢神经系统原始神经外胚层肿瘤（PNTR）。我们分析了9例散发性基底细胞癌和37例非散发性基底细胞癌的PTCH基因突变和表达。PTCH突变在3例基底细胞癌（33.3%）和5例髓母细胞瘤（14%）中发现，其中包括15例脑髓母细胞瘤，2/15例髓母细胞瘤和2/17例促结缔组织增生性髓母细胞瘤。这些肿瘤中的六个（四个PNIPs，两个BCC）的序列变化是预测导致截短蛋白质的突变。在一个PNET和一个BCC中检测到错义突变。此外，在PTCH的外显子2、内含子5、内含子10和内含子14中发现了新的序列多态性。逆转录-PCR分析显示PTCH表达水平增加相比，非肿瘤性脑组织和正常皮肤中的大多数PNAR和基底细胞癌的调查。我们的数据表明，PTCH的遗传改变不仅在遗传性和散发性基底细胞癌的意义，但也参与了一个子集的散发性中枢神经系统PNNs的分子发病机制。
The human homologue of the Drosophila segment polarity gene patched (PTCH) has recently been identified as the tumor suppressor gene responsible for the nevoid basal cell carcinoma (BCC) syndrome (H. Hahn et al., Cell, 85: 841-851, 1996; R. L. Johnson et al., Science (Washington DC), 272: 1668-1671, 1996). In addition to multiple BCCs, patients with nevoid BCC syndrome have a predisposition for the development of primitive neuroectodermal tumors (PNETs) of the central nervous system. We have analyzed 9 sporadic BCCs and 37 PNETs for mutation and expression of the PTCH gene. PTCH mutations were found in 3 BCCs (33.3%) and in 5 PNETs (14%), including 1 of 5 cerebral PNETs, 2 of 15 medulloblastomas, and 2 of 17 desmoplastic medulloblastomas. The sequence changes in six of these tumors (four PNETs, two BCCs) were mutations predicted to result in truncated proteins. Missense mutations were detected in one PNET and one BCC each. In addition, novel sequence polymorphisms were found in exon 2, intron 5, intron 10, and intron 14 of PTCH. Reverse transcription-PCR analysis revealed increased PTCH expression levels compared to nonneoplastic brain tissue and normal skin in the majority of PNETs and BCCs investigated. Our data suggest that genetic alterations of PTCH are not only of significance in hereditary and sporadic BCCs but are also involved in the molecular pathogenesis of a subset of sporadic central nervous system PNETs.