Amplified and homozygously deleted genes in glioblastoma: impact on gene expression levels

• Published in: PloS one 2012-09, Vol.7 (9), p.e46088
• Main Authors: Crespo, Inês, Tão, Hermínio, Nieto, Ana Belen, Rebelo, Olinda, Domingues, Patrícia, Vital, Ana Luísa, Patino, Maria del Carmen, Barbosa, Marcos, Lopes, Maria Celeste, Oliveira, Catarina Resende, Orfao, Alberto, Tabernero, María Dolores
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biology; Brain cancer; Cancer; Cell cycle; Chromosome 10; Chromosome 12; Chromosomes; Chromosomes, Human - genetics; Copy number; Deoxyribonucleic acid; DNA; Epidermal growth factor receptors; Female; Gene amplification; Gene Deletion; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene polymorphism; Genes; Genetic aspects; Genomes; Glioblastoma; Glioblastoma - genetics; Glioblastoma multiforme; Glioblastomas; Homozygote; Humans; Kinases; Male; Medical research; Medicine; Middle Aged; Mutation; Neurosciences; Neurosurgery; Pharmacy; Polymorphism; Polymorphism, Single Nucleotide; Ribonucleic acid; RNA; RNA, Messenger - genetics; Single nucleotide polymorphisms; Single-nucleotide polymorphism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0046088

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.