Retention of imprinting of the human apoptosis-related gene TSSC3 in human brain tumors
Retention of imprinting of the human apoptosis-related gene TSSC3 in human brain tumors
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DOI：
10.1093/hmg/9.5.757
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发表时间：
2000-03-22
影响因子：
3.5
通讯作者：
Zumkeller, W
中科院分区：
文献类型：
--
作者：
M端ller, S;van den Boom, D;Zumkeller, W
基因组印记是配子特异性修饰的结果，导致后代体细胞中亲本来源特异性基因表达。几种胚胎性肿瘤显示聚集在人类染色体11p15.5的基因印迹缺失，该区域是一个重要的肿瘤抑制基因区域，包含几个正常印迹基因，TSSC 3，一个与小鼠TDAG 51同源的基因，涉及Fas介导的凋亡，也位于hNAP 2和p57（KlP 2）之间的该区域，TSSC 3是第一个发现在胎盘中印迹的凋亡相关基因，肝脏和胎儿组织，其中它从人类正常发育中的母体等位基因表达。本研究调查了TSSC 3在正常人、成人脑以及人神经母细胞瘤、髓母细胞瘤和胶质母细胞瘤中的印迹状态。外显子1第54位的多态性被用来分析TSSC 3基因的等位基因表达的引物寡碱基延伸（PROBE）分析使用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）。我们发现TSSC 3基因在正常成人大脑和血液中没有印记。相反，在大多数检查的肿瘤标本中可以检测到类似印迹的强等位基因偏倚。研究结果首次证明，研究中的肿瘤与潜在生长抑制基因的印记保留有关。
Genomic imprinting is the result of a gamete-specific modification leading to parental origin-specific gene expression in somatic cells of the offspring. Several embryonal tumors show loss of imprinting of genes clustered in human chromosome 11p15.5, an important tumor suppressor gene region, harboring several normally imprinted genes, TSSC3, a gene homologous to mouse TDAG51, implicated in Fas-mediated apoptosis, is also located in this region between hNAP2 and p57(KlP2), TSSC3 is the first apoptosis-related gene found to be imprinted in placenta, liver and fetal tissues where it is expressed from the maternal allele in normal human development. This study investigated the imprinting status of TSSC3 in human normal, adult brain and in human neuroblastomas, medulloblastomas and glioblastomas. A polymorphism in exon 1 at position 54 was used to analyze the allelic expression of the TSSC3 gene by a primer oligo base extension (PROBE) assay using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). We found that the TSSC3 gene is not imprinted in human normal, adult brain and blood. In contrast, strong allelic bias resembling imprinting could be detected in most examined tumor specimens. The results demonstrate for the first time that the tumors under investigation are associated with a retention of imprinting of a potential growth inhibitory gene.