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Glioblastomas with copy number gains in EGFR and RNF139 show increased expressions of carbonic anhydrase genes transformed by ENO1.


ABSTRACT:

Background

Prominence of glycolysis in glioblastomas may be non-specific or a feature of oncogene-related subgroups (i.e. amplified EGFR, etc.). Relationships between amplified oncogenes and expressions of metabolic genes associated with glycolysis, directly or indirectly via pH, were therefore investigated.

Methods

Using multiplex ligation-dependent probe amplification, copy numbers (CN) of 78 oncogenes were quantified in 24 glioblastomas. Related expressions of metabolic genes encoding lactate dehydrogenases (LDHA, LDHC), carbonic anhydrases (CA3, CA12), monocarboxylate transporters (SLC16A3 or MCT4, SLC16A4 or MCT5), ATP citrate lyase (ACLY), glycogen synthase1 (GYS1), hypoxia inducible factor-1A (HIF1A), and enolase1 (ENO1) were determined in 22 by RT-qPCR. To obtain supra-glycolytic levels and adjust for heterogeneity, concurrent ENO1 expression was used to mathematically transform the expression levels of metabolic genes already normalized with delta-delta crossing threshold methodology.

Results

Positive correlations with EGFR occurred for all metabolic genes. Significant differences (Wilcoxon Rank Sum) for oncogene CN gains in tumors of at least 2.00-fold versus less than 2.00-fold occurred for EGFR with CA3's expression (p < 0.03) and for RNF139 with CA12 (p < 0.004). Increased CN of XIAP associated negatively. Tumors with less than 2.00-fold CN gains differed from those with gains for XIAP with CA12 (p < 0.05). Male gender associated with CA12 (p < 0.05).

Conclusions

Glioblastomas with CN increases in EGFR had elevated CA3 expression. Similarly, tumors with RNF149 CN gains had elevated CA12 expression.

General significance

In larger studies, subgroups of glioblastomas may emerge according to oncogene-related effects on glycolysis, such as control of pH via effects on carbonic anhydrases, with prognostic and treatment implications.

SUBMITTER: Beckner ME 

PROVIDER: S-EPMC4802406 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Glioblastomas with copy number gains in EGFR and RNF139 show increased expressions of carbonic anhydrase genes transformed by ENO1.

Beckner Marie E ME   Pollack Ian F IF   Nordberg Mary L ML   Hamilton Ronald L RL  

BBA clinical 20151110


<h4>Background</h4>Prominence of glycolysis in glioblastomas may be non-specific or a feature of oncogene-related subgroups (i.e. amplified EGFR, etc.). Relationships between amplified oncogenes and expressions of metabolic genes associated with glycolysis, directly or indirectly via pH, were therefore investigated.<h4>Methods</h4>Using multiplex ligation-dependent probe amplification, copy numbers (CN) of 78 oncogenes were quantified in 24 glioblastomas. Related expressions of metabolic genes e  ...[more]

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