Centre for Neuroscience and Cell Biology, University of Coimbra, Portugal.
PLoS One. 2012;7(9):e46088. doi: 10.1371/journal.pone.0046088. Epub 2012 Sep 28.
Glioblastoma multiforme (GBM) displays multiple amplicons and homozygous deletions that involve relevant pathogenic genes and other genes whose role remains unknown.
Single-nucleotide polymorphism (SNP)-arrays were used to determine the frequency of recurrent amplicons and homozygous deletions in GBM (n = 46), and to evaluate the impact of copy number alterations (CNA) on mRNA levels of the genes involved.
Recurrent amplicons were detected for chromosomes 7 (50%), 12 (22%), 1 (11%), 4 (9%), 11 (4%), and 17 (4%), whereas homozygous deletions involved chromosomes 9p21 (52%) and 10q (22%). Most genes that displayed a high correlation between DNA CNA and mRNA levels were coded in the amplified chromosomes. For some amplicons the impact of DNA CNA on mRNA expression was restricted to a single gene (e.g., EGFR at 7p11.2), while for others it involved multiple genes (e.g., 11 and 5 genes at 12q14.1-q15 and 4q12, respectively). Despite homozygous del(9p21) and del(10q23.31) included multiple genes, association between these DNA CNA and RNA expression was restricted to the MTAP gene.
Overall, our results showed a high frequency of amplicons and homozygous deletions in GBM with variable impact on the expression of the genes involved, and they contributed to the identification of other potentially relevant genes.
多形性胶质母细胞瘤（GBM）表现出多个扩增子和纯合性缺失，涉及相关的致病基因和其他作用未知的基因。
单核苷酸多态性（SNP）-阵列用于确定 GBM 中反复出现的扩增子和纯合性缺失的频率（n=46），并评估拷贝数改变（CNA）对涉及基因的 mRNA 水平的影响。
检测到染色体 7（50%）、12（22%）、1（11%）、4（9%）、11（4%）和 17（4%）的反复扩增子，而纯合性缺失涉及染色体 9p21（52%）和 10q（22%）。显示 DNA CNA 和 mRNA 水平之间高度相关性的大多数基因都编码在扩增的染色体中。对于一些扩增子，DNA CNA 对 mRNA 表达的影响仅限于单个基因（例如，7p11.2 处的 EGFR），而对于其他扩增子，则涉及多个基因（例如，12q14.1-q15 和 4q12 处分别有 11 个和 5 个基因）。尽管 9p21 纯合缺失和 10q23.31 缺失包含多个基因，但这些 DNA CNA 与 RNA 表达之间的关联仅限于 MTAP 基因。
总的来说，我们的研究结果显示 GBM 中扩增子和纯合性缺失的频率较高，对涉及的基因表达有不同的影响，并有助于鉴定其他潜在相关基因。
