Loss of the NF2 gene and merlin occur by the tumorlet stage of schwannoma development in neurofibromatosis 2.
Loss of the NF2 gene and merlin occur by the tumorlet stage of schwannoma development in neurofibromatosis 2.
复制标题
神经纤维瘤病 2 中神经鞘瘤发育的小瘤阶段会发生 NF2 基因和 merlin 的缺失。
DOI：
10.1097/00005072-199812000-00008
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发表时间：
1998
影响因子：
3.2
通讯作者：
Louis,DN
中科院分区：
文献类型：
--
作者：
Stemmer-Rachamimov,AO;Ino,Y;Lim,ZY;Jacoby,LB;MacCollin,M;Gusella,JF;Ramesh,V;Louis,DN
神经纤维瘤病2（NF 2）基因编码的蛋白质merlin的丢失是散发性和NF 2相关神经鞘瘤的普遍发现。某些NF 2患者除了较大的、坦率的神经鞘瘤外，还可能在脊神经根形成许多微小的许旺细胞瘤，从而为研究许旺细胞瘤发生中NF 2基因/merlin缺失的时间提供了机会。我们研究了一个NF 2患者与生殖系NF 2基因移码突变谁有许多许旺细胞瘤和神经鞘瘤。显微标本DNA杂合性丢失研究表明，在小肿瘤和神经鞘瘤中染色体22 q的NF 2区域存在等位基因丢失。免疫组化进一步证实了merlin在小肿瘤和神经鞘瘤中的表达缺失，而在邻近神经中的表达完整。因此，在雪旺细胞肿瘤发生的早期，在小肿瘤阶段之前，NF 2等位基因和merlin的丢失都发生了。对这些患者的小肿瘤和神经鞘瘤的研究也可能提供一个机会来阐明神经鞘细胞病变随后生长成有症状的肿瘤的机制。
Loss of the neurofibromatosis 2 (NF2) gene-encoded protein merlin is a universal finding in sporadic and NF2-associated schwannomas. Certain NF2 patients may develop numerous minute Schwann cell tumorlets of the spinal nerve roots in addition to larger, frank schwannomas and thereby provide an opportunity to investigate the timing ofNF2gene/merlin loss in Schwann cell tumorigenesis. We studied an NF2 patient with a germlineNF2gene frameshift mutation who had many Schwann cell tumorlets and schwannomas. Loss of heterozygosity studies of DNA from microdissected specimens showed allelic loss of theNF2region of chromosome 22q in tumorlets as well as schwannomas. Immunohistochemistry further demonstrated loss of merlin expression in tumorlets as well as schwannomas, with intact expression in adjacent nerve. Thus, loss of bothNF2alleles and merlin occur early in Schwann cell tumorigenesis, before the tumorlet stage. The study of tumorlets and schwannomas in such patients may also provide an opportunity to elucidate mechanisms responsible for the subsequent growth of Schwann cell lesions into symptomatic tumors.