title: Amplified and homozygously deleted genes in glioblastoma: impact on gene expression levels.
abstract: BACKGROUND
  Glioblastoma multiforme (GBM) displays multiple amplicons and homozygous deletions that involve relevant pathogenic genes and other genes whose role remains unknown.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Neuroscience and Cell Biology, University of Coimbra, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Crespo
authors.forename: Hermínio
authors.initials: H
authors.lastname: Tão
authors.forename: Ana Belen
authors.initials: AB
authors.lastname: Nieto
authors.forename: Olinda
authors.initials: O
authors.lastname: Rebelo
authors.forename: Patrícia
authors.initials: P
authors.lastname: Domingues
authors.forename: Ana Luísa
authors.initials: AL
authors.lastname: Vital
authors.forename: Maria del Carmen
authors.initials: Mdel C
authors.lastname: Patino
authors.forename: Marcos
authors.initials: M
authors.lastname: Barbosa
authors.forename: Maria Celeste
authors.initials: MC
authors.lastname: Lopes
authors.forename: Catarina Resende
authors.initials: CR
authors.lastname: Oliveira
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Tabernero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D012333:RNA, Messenger