Martínez-Glez Victor, Alvarez Luis, Franco-Hernández Carmen, Torres-Martin Miguel, de Campos Jose M, Isla Alberto, Vaquero Jesús, Lassaletta Luis, Castresana Javier S, Casartelli Cacilda, Rey Juan A
Research Unit-Unidad de Investigación, Hospital Universiatrio La Paz, Paseo Castellana 261, 28046 Madrid, Spain.
Cancer Genet Cytogenet. 2010 Jan 1;196(1):1-6. doi: 10.1016/j.cancergencyto.2009.08.003.
The molecular pathology of meningiomas and shwannomas involve the inactivation of the NF2 gene to generate grade I tumors. Genomic losses at 1p and 14q are observed in both neoplasms, although more frequently in meningiomas. The inactivation of unidentified genes located in these regions appears associated with tumor progression in meningiomas, but no clues to its molecular/clinical meaning are available in schwannomas. Recent microarray gene expression studies have demonstrated the existence of molecular subgroups in both entities. In the present study, we correlated the presence of genomic deletions at 1p, 14q, and 22q with the expression patterns of 96 tumor-related genes obtained by cDNA low-density microarrays in a series of 65 tumors including 42 meningiomas and 23 schwannomas. Two expression pattern groups were identified by cDNA mycroarray analysis when compared to the expression pattern in normal control RNA in both meningiomas and schwannomas, each one with patterns similar and different from the normal control. Meningioma and schwannoma subgroups differed in the expression of 38 and 16 genes, respectively. Using MLPA and microsatellites, we identified genomic losses at 1p, 14q, and 22q at nonrandom frequencies (12.5-69%) in meningiomas and schwannomas. Losses at 22q were almost equally frequent in both molecular expression subgroups in both neoplasms. However, deletions at 1p and 14q accumulated in meningiomas with a gene expression pattern different from the normal pattern, whereas the inverse situation occurred in schwannomas. Those anomalies characterized the schwannomas with expression pattern similar to the normal control. These findings suggest that deletions at 1p and 14q enhance the development of an abnormal tumor-related gene expression pattern in meningiomas, but this fact is not corroborated in schwannomas.
脑膜瘤和神经鞘瘤的分子病理学涉及NF2基因失活以产生I级肿瘤。在这两种肿瘤中均观察到1p和14q的基因组缺失，不过在脑膜瘤中更为常见。位于这些区域的未明确基因的失活似乎与脑膜瘤的肿瘤进展相关，但在神经鞘瘤中尚无关于其分子/临床意义的线索。最近的微阵列基因表达研究表明这两种肿瘤均存在分子亚组。在本研究中，我们将1p、14q和22q处基因组缺失的存在情况与通过cDNA低密度微阵列获得的96个肿瘤相关基因的表达模式进行了关联分析，这96个基因来自于包括42例脑膜瘤和23例神经鞘瘤在内的65个肿瘤。与正常对照RNA的表达模式相比，通过cDNA微阵列分析在脑膜瘤和神经鞘瘤中均鉴定出两个表达模式组，每组的模式与正常对照相似或不同。脑膜瘤和神经鞘瘤亚组分别有38个和16个基因的表达存在差异。使用多重连接探针扩增（MLPA）和微卫星技术，我们在脑膜瘤和神经鞘瘤中以非随机频率（12.5 - 69%）鉴定出1p、14q和22q处的基因组缺失。在这两种肿瘤的两个分子表达亚组中，22q处的缺失频率几乎相同。然而，1p和14q处的缺失在基因表达模式与正常模式不同的脑膜瘤中积累，而在神经鞘瘤中情况相反。这些异常特征表现为神经鞘瘤的表达模式与正常对照相似。这些发现表明，1p和14q处的缺失促进了脑膜瘤中异常肿瘤相关基因表达模式的形成，但在神经鞘瘤中并未得到证实。
