Amplified and Homozygously Deleted Genes in Glioblastoma: Impact on Gene Expres...

• Autor(es): Crespo, I ; Tão, H ; Nieto, AB ; Rebelo, O ; Domingos, P ; Vital, AL ; Patino, MC ; Barbosa, MD ; Lopes, MC ; Resende de Oliveira, C ; Orfão, A ; Tabernero, MD
• Data: 2012
• Identificador Persistente: http://hdl.handle.net/10400.4/1528
• Origem: Repositório do Centro Hospitalar e Universitário de Coimbra
• Assunto(s): Glioblastoma; Homozigoto; Delecção do Gene; Regulação Neoplásica da Expressão Génica
• Tipo de Documento: Artigo
• Idioma: Inglês

Descrição

BACKGROUND: Glioblastoma multiforme (GBM) displays multiple amplicons and homozygous deletions that involve relevant pathogenic genes and other genes whose role remains unknown. METHODOLOGY: 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. PRINCIPAL FINDINGS: 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.