Bijlsma E K, Brouwer-Mladin R, Bosch D A, Westerveld A, Hulsebos T J
Institute of Human Genetics, University of Amsterdam, The Netherlands.
Genes Chromosomes Cancer. 1992 Oct;5(3):201-5. doi: 10.1002/gcc.2870050305.
Schwannomas are tumors of the cranial, spinal, and peripheral nerve sheaths that originate from Schwann cells. Acoustic neurinomas are the most frequent cranial schwannomas. They might develop sporadically or in the context of neurofibromatosis type 2 (NF2). Loss of part or all of chromosome 22 is frequently found in acoustic schwannomas, suggesting that the NF2 gene is a tumor suppressor gene involved in the genesis of these tumors. Only a few spinal schwannomas have been molecularly characterized so far, showing that chromosome 22 loss might also occur in these tumors. Here we present the molecular analysis of chromosome 22 in 23 acoustic schwannomas and nine schwannomas of other locations (including other cranial nerves and spinal and peripheral nerves). Most of these tumors were from sporadic cases. Multiple schwannomas of various locations were analyzed in two patients with NF2. We found partial or complete monosomy for chromosome 22 in 22% of the acoustic schwannomas and 55% of the non-acoustic schwannomas. The tumors with partial monosomy included four with terminal deletions and one with a deletion of the centromeric part of the long arm of chromosome 22. The region between the beta B2-1 crystallin locus (CRYB2A) and the myoglobin locus (MB) was commonly deleted in these tumors. Our studies suggest that a schwannoma-related tumor suppressor gene within this region, which might be the NF2 gene, is involved in the development of schwannomas of various locations in the nervous system. Our studies indicate that the second hit in the genesis of different schwannomas within one (predisposed) NF2 patient occurs independently and via different mechanisms.
施万细胞瘤是起源于施万细胞的颅神经、脊神经和周围神经鞘瘤。听神经瘤是最常见的颅神经施万细胞瘤。它们可能散发性发生，也可能在2型神经纤维瘤病（NF2）的背景下发生。在听神经瘤中经常发现22号染色体部分或全部缺失，这表明NF2基因是参与这些肿瘤发生的肿瘤抑制基因。到目前为止，只有少数脊神经施万细胞瘤进行了分子特征分析，表明这些肿瘤中也可能发生22号染色体缺失。在此，我们展示了对23例听神经瘤和9例其他部位（包括其他颅神经、脊神经和周围神经）施万细胞瘤的22号染色体的分子分析。这些肿瘤大多来自散发病例。对两名NF2患者的不同部位的多个施万细胞瘤进行了分析。我们发现22%的听神经瘤和55%的非听神经瘤存在22号染色体部分或完全单体性。部分单体性的肿瘤包括4例末端缺失和1例22号染色体长臂着丝粒部分缺失。在这些肿瘤中，βB2-1晶状体蛋白基因座（CRYB2A）和肌红蛋白基因座（MB）之间的区域通常缺失。我们的研究表明，该区域内一个与施万细胞瘤相关的肿瘤抑制基因，可能是NF2基因，参与了神经系统不同部位施万细胞瘤的发生。我们的研究表明，在一名（易感的）NF2患者中，不同施万细胞瘤发生过程中的第二次打击是独立发生的，且机制不同。
