Expression of Carbonic Anhydrase Genes, CA3 and CA12, Transformed with ENO1, Relate to Copy Numbers of EGFR or RNF139 and XIAP, and Gender in Glioblastomas Using PCR Assays

Abstract

Relationships between amplified oncogenes and glycolysis were studied in glioblastomas (GBs) using ENO1 to define supraphysiologic metabolic gene expressions. Copy numbers (CN) of 78 oncogenes were quantified in 24 GBs using multiplex ligation‐dependent probe amplification. Expressions were obtained in 22 by real‐time qPCR for genes encoding lactate dehydrogenases(LDHA, LDHC), carbonic anhydrases(CA3, CA12), monocarboxylate transporter(SLC16A3/MCT4), ATP citrate lyase(ACLY), glycogen synthase(GYS1) & enolase1(ENO1). Expressions were transformed by division with ENO1 expression after routine normalization. All GBs harbored oncogene gains. 20 oncogenes in 18 GBs were amplified at least 3X, up to 6/tumor, most frequently EGFR. Positive correlations with 6 oncogenes were shared by CA3, CA12, LDHC, LDHA, & SLC16A3, whereas + correlations with 5 different oncogenes were shared by ACLY, GYS1, LDHA, & LDHC. CN of XIAP correlated negatively. Differences (Wilcoxon Rank Sum) for >= 2X oncogene CN gains in GBs versus those without occurred for EGFR with CA3 (p<0.03) and RNF139 with CA12 (p<0.004). Difference for tumors with <2X CN gains versus those with gains occurred for XIAP with CA12 (p<0.05). Male gender associated with CA12 (p<0.02). Thus, transformation by ENO1 revealed strong relationships between genes encoding carbonic anhydrases and EGFR, RNF139, XIAP, and gender in GBs. The Pittsburgh Foundation Walter L. Copeland Fund for Cranial Research & Louisiana State Univ Hlth Sci Cen in Shreveport Grant‐in‐Aid.