Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
J Mol Diagn. 2011 Nov;13(6):634-47. doi: 10.1016/j.jmoldx.2011.06.003. Epub 2011 Aug 30.
Glioblastomas are cytogenetically heterogeneous tumors that frequently display alterations of chromosomes 7, 9p, and 10q. We used high-density (500K) single-nucleotide polymorphism arrays to investigate genome-wide copy number alterations and loss of heterozygosity in 35 primary glioblastomas. We focused on the identification and detailed characterization of alterations involving the most frequently altered chromosomes (chromosomes 7, 9, and 10), the identification of distinct prognostic subgroups of glioblastomas based on the cytogenetic patterns of alteration for these chromosomes, and validation of their prognostic impact in a larger series of tumors from public databases. Gains of chromosome 7 (97%), with or without epidermal growth factor receptor (EGFR) amplification, and losses of chromosomes 9p (83%) and 10 (91%) were the most frequent alterations. Such alterations defined five different cytogenetic groups with a significant effect on patient survival; notably, EGFR amplification (29%) was associated with a better survival among older patients, as confirmed by multivariate analysis of a larger series of glioblastomas from the literature. In addition, our results provide further evidence about the relevance of other genes (eg, EGFR, CDKN2A/B, MTAP) in the pathogenesis of glioblastomas. Altogether, our results confirm the cytogenetic heterogeneity of glioblastomas and suggest that their stratification based on combined assessment of cytogenetic alterations involving chromosomes 7, 9, and 10 may contribute to the prognostic evaluation of glioblastomas.
胶质母细胞瘤是细胞遗传学上异质性的肿瘤,经常显示染色体 7、9p 和 10q 的改变。我们使用高密度(500K)单核苷酸多态性微阵列来研究 35 例原发性胶质母细胞瘤的全基因组拷贝数改变和杂合性丢失。我们专注于鉴定和详细描述涉及最常改变的染色体(染色体 7、9 和 10)的改变,基于这些染色体改变的细胞遗传学模式鉴定胶质母细胞瘤的不同预后亚组,并在来自公共数据库的更大系列肿瘤中验证其预后影响。染色体 7 的增益(97%),无论是否有表皮生长因子受体(EGFR)扩增,以及染色体 9p(83%)和 10(91%)的丢失是最常见的改变。这些改变定义了五个不同的细胞遗传学组,对患者的生存有显著影响;值得注意的是,EGFR 扩增(29%)与老年患者的生存改善相关,这在对来自文献的更大系列胶质母细胞瘤的多变量分析中得到了证实。此外,我们的结果提供了进一步的证据,证明了其他基因(如 EGFR、CDKN2A/B、MTAP)在胶质母细胞瘤发病机制中的相关性。总之,我们的结果证实了胶质母细胞瘤的细胞遗传学异质性,并表明基于涉及染色体 7、9 和 10 的细胞遗传学改变的综合评估对胶质母细胞瘤的预后评估可能有帮助。