A potential role for co‐amplification of other oncogenes with EGFR in the control of metabolism in glioblastomas

• Published in: The FASEB journal 2011-04, Vol.25 (S1), p.lb318-lb318
• Main Authors: Beckner, Marie E, Kant, Jeffrey A, Pollack, Ian F, Nordberg, Mary L, Hamilton, Ronald L
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.25.1_supplement.lb318

Based on EGFR's frequent amplification in glioblastomas, gains in copy numbers for it and other oncogenes were investigated for associations with expression of genes that encode mediators of glycolysis. ATP citrate lyase (ACLY) was included due to its protein's cleavage of cytosolic citric acid, a glycolysis inhibitor. RNA and DNA were isolated from 22 glioblastomas (adults) and analyzed with real‐time quantitative PCR (RT‐qPCR) and multiplex ligation‐dependent probe amplification (MLPA). Transcript levels of ACLY, enolase 1 (ENO1), and other genes were analyzed with delta delta crossing threshold methodology. RT‐qPCR results were normalized with actin B and glyceraldehyde phosphate dehydrogenase using normal brain RNA. Expression of ACLY correlated well with ENO1. MLPA data for 78 oncogenes were normalized against normal DNA. At least 15 oncogenes showed ≥3‐fold amplifications in 14 of 22 glioblastomas. FISH confirmed results for EGFR in 18 cases tested. EGFR was amplified alone and combined with other oncogenes in 7 & 4 tumors, respectively. A trend (p = 0.1167, Fisher exact test) was detected for increased ACLY expression when EGFR was co‐amplified with CDK6, CDK4, MOS, CYP27B1 &/or PDGFRA, but not alone. Co‐amplification of other oncogenes with EGFR may correlate with regulation of glycolysis.