Wozniak K, Piaskowski S, Gresner S M, Golanska E, Bieniek E, Bigoszewska K, Sikorska B, Szybka M, Kulczycka-Wojdala D, Zakrzewska M, Zawlik I, Papierz W, Stawski R, Jaskolski D J, Och W, Sieruta M, Liberski P P, Rieske P
Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Czechoslowacka 8/10, 92-216 Lodz, Poland.
Cancer Genet Cytogenet. 2008 May;183(1):14-20. doi: 10.1016/j.cancergencyto.2008.01.020.
Neurofibromin 2 (NF2), located on chromosome arm 22q, has been established as a tumor suppressor gene involved in meningioma pathogenesis. In our study, we investigated 149 meningiomas to determine whether there are additional tumor suppressor genes localized on chromosome 22q, apart from NF2, that might be involved in meningioma pathogenesis. The LOH analysis on chromosome 22q identified two regions of deletion: the first one, which is limited to the NF2 gene locus, and the second one, which is outside this location. The new minimal deletion region (MDR) included the following genes: BCR (breakpoint cluster region), RAB36 (a member of RAS oncogene family), GNAZ [guanine nucleotide binding protein (G protein), alpha-z polypeptide], and RTDR1 (rhabdoid tumor deletion region gene 1). The expression levels of all these genes, including NF2, were subsequently analyzed by quantitative real-time polymerase chain reaction. We observed a significantly lowered expression level of NF2 in meningiomas with 22q loss of heterozygosity (LOH) within NF2 region compared to the one in meningiomas with 22q retention of heterozygosity (ROH, P<0.05). Similarly, BCR showed a significantly lowered expression in meningiomas with 22q LOH within the new MDR compared to cases with 22q ROH (P<0.05). Our data, together with the already published information considering BCR function suggest that BCR can be considered as a candidate tumor suppressor gene localized on chromosome 22q which may be involved in meningioma pathogenesis.
神经纤维瘤病2型（NF2）定位于22号染色体长臂，已被确认为参与脑膜瘤发病机制的肿瘤抑制基因。在我们的研究中，我们调查了149例脑膜瘤，以确定除NF2外，22号染色体上是否存在其他可能参与脑膜瘤发病机制的肿瘤抑制基因。对22号染色体的杂合性缺失（LOH）分析确定了两个缺失区域：第一个区域局限于NF2基因座，第二个区域位于该位置之外。新的最小缺失区域（MDR）包括以下基因：BCR（断裂点簇集区域）、RAB36（RAS癌基因家族成员）、GNAZ[鸟嘌呤核苷酸结合蛋白（G蛋白），α-z多肽]和RTDR1（横纹肌瘤缺失区域基因1）。随后通过定量实时聚合酶链反应分析了所有这些基因（包括NF2）的表达水平。我们观察到，与22号染色体杂合性保留（ROH）的脑膜瘤相比，NF2区域发生22号染色体杂合性缺失（LOH）的脑膜瘤中NF2的表达水平显著降低（P<0.05）。同样，与22号染色体ROH的病例相比，新MDR内发生22号染色体LOH的脑膜瘤中BCR的表达显著降低（P<0.05）。我们的数据，连同已发表的关于BCR功能的信息表明，BCR可被视为定位于22号染色体上可能参与脑膜瘤发病机制的候选肿瘤抑制基因。
