Brinkschmidt C, Christiansen H, Terpe H J, Simon R, Boecker W, Lampert F, Stoerkel S
Gerhard-Domagk-Institute of Pathology, University of Münster, Germany.
J Pathol. 1997 Apr;181(4):394-400. doi: 10.1002/(SICI)1096-9896(199704)181:4<394::AID-PATH800>3.0.CO;2-1.
Comparative genomic hybridization (CGH) was applied to 35 neuroblastomas to obtain a global view of genetic imbalances. Results were validated by means of Southern blot hybridization (detection of N-myc amplification), loss of heterozygosity (LOH) studies (detection of deletion 1p), and interphase cytogenetics [dual labelling fluorescence in situ hybridization (FISH) of centromeric 17 and erbB-2]. CGH allowed sensitive detection of N-myc amplification and chromosome 1p deletion, representing the most established prognostic markers of neuroblastoma. In addition, a high rate of chromosome 17 aberrations (63 per cent) with possible prognostic relevance was observed. Previously unreported high level copy number increases indicating oncogene amplification were mapped to chromosome subbands 2p13-14 and 3q24-26. Other recurrent regional chromosomal aberrations were localized on 11q, 12q, 13q, 14q, and 15q. CGH results were fully consistent with data of Southern blot analysis and LOH study, as well as interphase cytogenetics. These results show that CGH is a sensitive method for the detection of all prognostically relevant genetic alterations in neuroblastomas; that CGH considerably simplifies the detection of these alterations, resulting in a single methodological approach; and that CGH is a powerful tool to elucidate previously unknown genetic changes in neuroblastomas.
采用比较基因组杂交(CGH)技术对35例神经母细胞瘤进行检测,以全面了解基因失衡情况。通过Southern印迹杂交(检测N-myc扩增)、杂合性缺失(LOH)研究(检测1p缺失)和间期细胞遗传学[着丝粒17和erbB-2的双标记荧光原位杂交(FISH)]对结果进行验证。CGH能够灵敏地检测出N-myc扩增和1号染色体p臂缺失,这是神经母细胞瘤最确定的预后标志物。此外,还观察到17号染色体畸变率较高(63%),可能具有预后相关性。此前未报道的表明癌基因扩增的高水平拷贝数增加定位于染色体亚带2p13 - 14和3q24 - 26。其他复发性区域染色体畸变定位于11q、12q、13q、14q和15q。CGH结果与Southern印迹分析、LOH研究以及间期细胞遗传学数据完全一致。这些结果表明,CGH是检测神经母细胞瘤所有预后相关基因改变的灵敏方法;CGH大大简化了这些改变的检测,形成了单一的方法学途径;并且CGH是阐明神经母细胞瘤中先前未知基因变化的有力工具。