Brinkschmidt C, Poremba C, Christiansen H, Simon R, Schäfer K L, Terpe H J, Lampert F, Boecker W, Dockhorn-Dworniczak B
Gerhard-Domagk-Institute of Pathology, University of Münster, Germany.
Br J Cancer. 1998 Jun;77(12):2223-9. doi: 10.1038/bjc.1998.370.
Chromosomal aberrations of 20 stage 4s neuroblastomas were analysed by comparative genomic hybridization (CGH). In a subset of 13/20 tumours, telomerase activity was evaluated by the telomeric repeat amplification protocol (TRAP). The CGH data were compared with the CGH results of ten stage 1 and 2 (stage 1/2) and 22 stage 3 and 4 (stage 3/4) neuroblastomas. A total of 17/20 stage 4s neuroblastomas did not progress clinically, whereas tumour progression with lethal outcome occurred in 3/20 cases. The CGH data of clinically non-progressing stage 4s tumours revealed a high rate of whole-chromosome aberrations (73.4%) with an overrepresentation of mainly chromosomes 2, 6, 7, 12, 13, 17, 18 and an underrepresentation of mainly chromosomes 3, 4, 11, 14. MYCN amplification or 1p deletion was observed in only 1/27 or 2/17 clinically non-progressing stage 4s tumours respectively, whereas all three progressive stage 4s neuroblastomas showed MYCN amplification, 1p deletion and, in 2/3 cases, distal 17q gains. Except for one case, telomerase activity was not observed in non-progressing stage 4s neuroblastomas. In contrast, 4s tumours with lethal outcome revealed elevated telomerase activity levels. Our data suggest that stage 4s neuroblastomas belong to two biologically different groups, one of which displays the genetic features of localized stage 1/2 tumours, whereas the other mimics advanced stage 3/4 neuroblastomas.
采用比较基因组杂交（CGH）技术分析了20例4s期神经母细胞瘤的染色体畸变情况。在20例肿瘤中的13例亚组中，通过端粒重复序列扩增法（TRAP）评估了端粒酶活性。将CGH数据与10例1期和2期（1/2期）以及22例3期和4期（3/4期）神经母细胞瘤的CGH结果进行了比较。20例4s期神经母细胞瘤中共有17例临床未进展，而20例中有3例发生肿瘤进展并导致致命后果。临床未进展的4s期肿瘤的CGH数据显示全染色体畸变率较高（73.4%），主要是2号、6号、7号、12号、13号、17号、18号染色体增加，主要是3号、4号、11号、14号染色体减少。在临床未进展的4s期肿瘤中，分别仅在1/27例或2/17例中观察到MYCN扩增或1p缺失，而所有3例进展期4s期神经母细胞瘤均显示MYCN扩增、1p缺失，并且在2/3例中显示17q远端增加。除1例病例外，临床未进展的4s期神经母细胞瘤未观察到端粒酶活性。相比之下，有致命后果的4s期肿瘤显示端粒酶活性水平升高。我们的数据表明，4s期神经母细胞瘤属于两个生物学上不同的组，其中一组表现出局限性1/2期肿瘤的遗传特征，而另一组则类似于晚期3/4期神经母细胞瘤。
