Pećina-Slaus Nives, Niku Eva-Martić Tamara, Beros Vili, Tomas Davor
Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia.
Pathol Oncol Res. 2007;13(4):370-4. doi: 10.1007/BF02940319. Epub 2007 Dec 25.
The genetic basis as well as mechanisms of development of germ cell tumors of the CNS are still unexplained. In the present article changes of Ecadherin (CDH1) and beta-catenin (CTNNB1) genes in two CNS germ cell tumors are reported. Both gene products are components of adherens junctions, but are also involved in the Wnt signaling pathway. A case of germinoma of the central nervous system and a case of spinal channel teratoma were tested for loss of heterozygosity (LOH) of E-cadherin gene by PCR amplification of tetranucleotide polymorphism (D16S752). Changes of beta-catenin were tested by heteroduplex method. Both germ cell tumors analyzed demonstrated LOH of the CDH1 gene. Analysis of exon 3 of the CTNNB1 gene showed additional band in the germinoma, suggesting that this sample harbors mutation in the beta-catenin gene. Immunostaining showed that LOHs in our samples were accompanied with the absence of E-cadherin protein. We also investigated E-cadherin expression in four other germinomas, of which three were negative and one was mildly positive. Our findings may contribute to better understanding of the genetic profile of germ cell tumors.
中枢神经系统生殖细胞肿瘤的遗传基础以及发生机制仍不清楚。在本文中,报道了两种中枢神经系统生殖细胞肿瘤中E-钙黏蛋白(CDH1)和β-连环蛋白(CTNNB1)基因的变化。这两种基因产物都是黏附连接的组成成分,但也参与Wnt信号通路。通过对四核苷酸多态性(D16S752)进行PCR扩增,检测了1例中枢神经系统生殖细胞瘤和1例脊髓管畸胎瘤中E-钙黏蛋白基因的杂合性缺失(LOH)。通过异源双链法检测β-连环蛋白的变化。所分析的两种生殖细胞肿瘤均显示CDH1基因存在杂合性缺失。对CTNNB1基因第3外显子的分析显示,生殖细胞瘤中有额外条带,提示该样本的β-连环蛋白基因存在突变。免疫染色显示,我们样本中的杂合性缺失伴随着E-钙黏蛋白的缺失。我们还研究了另外4例生殖细胞瘤中E-钙黏蛋白的表达情况,其中3例为阴性,1例为弱阳性。我们的研究结果可能有助于更好地了解生殖细胞肿瘤的基因特征。