Mérel P, Hoang-Xuan K, Sanson M, Moreau-Aubry A, Bijlsma E K, Lazaro C, Moisan J P, Resche F, Nishisho I, Estivill X
Laboratoire de Génétique des Tumeurs, INSERM U434, Institut Curie, Paris, France.
Genes Chromosomes Cancer. 1995 Jul;13(3):211-6. doi: 10.1002/gcc.2870130311.
The NF2 gene is a putative tumor-suppressor gene that, when it is altered in the germline, causes neurofibromatosis type 2, a tumor-susceptibility disease that mainly predisposes to schwannomas and meningiomas. The recent isolation of the NF2 gene on chromosome 22 allows the identification of somatic mutations in human tumors. We have searched for mutations of the NF2 gene in 331 primary human tumors using a screening method based on denaturing gradient gel electrophoresis, which allows the detection of mutations in 95% of the coding sequence. Mutations were observed in 17 of 57 meningiomas and in 30 of 89 schwannomas. No mutations were observed for 17 ependymomas, 70 gliomas, 23 primary melanomas, 24 pheochromocytomas, 15 neuroblastomas, 6 medulloblastomas, 15 colon cancers, and 15 breast cancers. All meningiomas and one-half of the schwannomas with identified NF2 mutations demonstrated chromosome 22 allelic losses. We conclude that the involvement of the NF2 gene in human tumorigenesis may be restricted to schwannomas and meningiomas, where it is frequently inactivated by a two-hit process.
NF2基因是一种推定的肿瘤抑制基因，当其在种系中发生改变时，会导致2型神经纤维瘤病，这是一种肿瘤易感性疾病，主要易患神经鞘瘤和脑膜瘤。最近在22号染色体上分离出NF2基因，使得能够鉴定人类肿瘤中的体细胞突变。我们使用基于变性梯度凝胶电泳的筛选方法，在331例原发性人类肿瘤中寻找NF2基因的突变，该方法能够检测95%的编码序列中的突变。在57例脑膜瘤中的17例以及89例神经鞘瘤中的30例中观察到了突变。在17例室管膜瘤、70例胶质瘤、23例原发性黑色素瘤、24例嗜铬细胞瘤、15例神经母细胞瘤、6例髓母细胞瘤、15例结肠癌和15例乳腺癌中未观察到突变。所有检测到NF2基因突变的脑膜瘤以及一半的神经鞘瘤都显示出22号染色体等位基因缺失。我们得出结论，NF2基因在人类肿瘤发生中的作用可能仅限于神经鞘瘤和脑膜瘤，在这些肿瘤中它经常通过双打击过程而失活。
