Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-75185, Uppsala, Sweden.
J Neurooncol. 2012 Mar;107(1):37-49. doi: 10.1007/s11060-011-0716-0. Epub 2011 Oct 7.
Medulloblastoma (MB) is a WHO grade IV, invasive embryonal CNS tumor that mainly affects children. The aggressiveness and response to therapy can vary considerably between cases, and despite treatment, ~30% of patients die within 2 years from diagnosis. Furthermore, the majority of survivors suffer long-term side-effects due to severe management modalities. Several distinct morphological features have been associated with differences in biological behavior, but improved molecular-based criteria that better reflect the underlying tumor biology are in great demand. In this study, we profiled a series of 25 MB with a 32K BAC array covering 99% of the current assembly of the human genome for the identification of genetic copy number alterations possibly important in MB. Previously known aberrations as well as several novel focally amplified loci could be identified. As expected, the most frequently observed alteration was the combination of 17p loss and 17q gain, which was detected in both high- and standard-risk patients. We also defined minimal overlapping regions of aberrations, including 16 regions of gain and 18 regions of loss in various chromosomes. A few noteworthy narrow amplified loci were identified on autosomes 1 (38.89-41.97 and 84.89-90.76 Mb), 3 (27.64-28.20 and 35.80-43.50 Mb), and 8 (119.66-139.79 Mb), aberrations that were verified with an alternative platform (Illumina 610Q chips). Gene expression levels were also established for these samples using Affymetrix U133Plus2.0 arrays. Several interesting genes encompassed within the amplified regions and presenting with transcript upregulation were identified. These data contribute to the characterization of this malignant childhood brain tumor and confirm its genetic heterogeneity.
髓母细胞瘤(MB)是一种 WHO 分级 IV 级、侵袭性胚胎性中枢神经系统肿瘤,主要影响儿童。尽管进行了治疗,但约 30%的患者在诊断后 2 年内死亡。此外,由于严重的治疗方式,大多数幸存者都长期遭受副作用。已经有几个不同的形态特征与生物学行为的差异相关,但需要更好地反映肿瘤生物学基础的改进的基于分子的标准。在这项研究中,我们对 25 例 MB 进行了分析,使用了一个 32K BAC 阵列,该阵列覆盖了人类基因组当前组装的 99%,以鉴定可能对 MB 重要的遗传拷贝数改变。可以识别出以前已知的畸变以及几个新的局部扩增基因座。正如预期的那样,最常观察到的改变是 17p 缺失和 17q 增益的组合,在高风险和标准风险患者中均有检测到。我们还定义了最小的畸变重叠区域,包括各个染色体上的 16 个增益区和 18 个缺失区。在常染色体 1(38.89-41.97 和 84.89-90.76 Mb)、3(27.64-28.20 和 35.80-43.50 Mb)和 8(119.66-139.79 Mb)上鉴定出了几个值得注意的狭窄扩增基因座,这些畸变通过替代平台(Illumina 610Q 芯片)进行了验证。还使用 Affymetrix U133Plus2.0 阵列为这些样本建立了基因表达水平。鉴定出了一些包含在扩增区域内并呈现转录上调的有趣基因。这些数据有助于对这种恶性儿童脑肿瘤进行特征描述,并证实其遗传异质性。