van Dartel Maaike, Leenstra Sieger, Troost Dirk, Hulsebos Theo J M
Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Cancer Genet Cytogenet. 2003 Jan 15;140(2):162-6. doi: 10.1016/s0165-4608(02)00683-0.
We reported previously the amplification of DNA markers in 17p12 in 3 of 60 high-grade gliomas. To detect additional cases, we screened in total 104 gliomas of various types and grades by Southern blot analysis using marker 745R, which is within the commonly amplified region. However, no other caseswith significant amplification (amplification level > 4) were found. To investigate in detail the extent of the amplifications in the three tumors, which were all glioblastomas, we determined 17p11.2 approximately p12 amplification profiles by semiquantitative polymerase chain reaction using 15 microsatellite markers and seven candidate genes. Distinct and high-level amplifications, with maximum levels ranging from 15 to 38, were found in these tumors. The 0.8 Mb-region between D17S1525 and MAP2K4 in 17p12 proved to be commonly amplified in these tumors. In one tumor, a heterogeneous distribution of the amplification in 17p12 was found, suggesting that it is a late event during glioma tumorigenesis. Another tumor showed additional high-level amplification of PMP22 and D17S1843 in 17p11.2. From the high-level amplifications we conclude that at least one, but possibly more, putative oncogenes are present in 17p11.2 approximately p12 whose amplifications and/or overexpressions contribute to glioma tumorigenesis.
我们先前报道了在60例高级别胶质瘤中有3例存在17p12区域的DNA标记物扩增。为了检测更多病例，我们使用位于常见扩增区域内的标记物745R，通过Southern印迹分析对总共104例不同类型和级别的胶质瘤进行了筛查。然而，未发现其他有显著扩增（扩增水平>4）的病例。为了详细研究这三例均为胶质母细胞瘤的肿瘤的扩增范围，我们使用15个微卫星标记和7个候选基因，通过半定量聚合酶链反应确定了17p11.2至大约p12的扩增图谱。在这些肿瘤中发现了明显的高水平扩增，最高水平范围为15至38。17p12中D17S1525和MAP2K4之间的0.8 Mb区域在这些肿瘤中被证明是常见扩增区域。在一个肿瘤中，发现17p12区域的扩增呈异质性分布，这表明它是胶质瘤发生过程中的一个晚期事件。另一个肿瘤在17p11.2区域显示出PMP22和D17S1843的额外高水平扩增。从高水平扩增我们得出结论，在17p11.2至大约p12区域中至少存在一个，但可能更多的推定癌基因，其扩增和/或过表达促进了胶质瘤的发生。
