Proteomic comparison of oligodendrogliomas with and without 1pLOH.
OBJECTIVE
Chemoresistance is a widespread therapeutic challenge in glial tumors. The molecular basis of chemoresistance is poorly understood, precluding advances in glioma treatment and leaving gliomas among the most lethal tumors. Oligodendrogliomas provide a unique model to study the molecular basis of chemoresistance, as there are two distinct genetic subtypes with significant differences in chemosensitivity. Despite a high morphological similarity, tumors with allelic loss on the short arm of chromosome 1 (1pLOH) are more chemosensitive than those without 1pLOH.


METHODS
In order to identify candidate proteins potentially responsible for glioma chemosensitivity, we compared the proteome of four oligodendrogliomas with and five without 1pLOH using comparative proteomic profiling. Proteomic analysis was performed by two-dimensional protein gel electrophoresis and subsequent computerized gel analysis for detection of distinguishing patterns of protein expression. Differentially expressed proteins were identified using Liquid Chromatography/Mass Spectrometry. Differential expression of select proteins was confirmed by Western blotting.


RESULTS
We identified seven candidate proteins that are overexpressed in oligodendrogliomas without 1pLOH. Two of these proteins (glyoxalase I and Rho GDP dissociation inhibitor) have previously been shown to enhance chemoresistance in other tumors. In turn, we identified twelve overexpressed proteins in tumors with 1pLOH that have previously been reported to induce chemosensitivity in other forms of human neoplasia.


CONCLUSIONS
These identified proteins are potential targets for pharmacological therapy and may also be useful as biomarkers for differentiation of chemoresistant and chemosensitive oligodendroglioma.
Okamoto
Hiroaki
H
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland 20892-1414, USA.
Li
Jie
J
Gläsker
Sven
S
Vortmeyer
Alexander O
AO
Jaffe
Howard
H
Robison
R Aaron
RA
Bogler
Oliver
O
Mikkelsen
Tom
T
Lubensky
Irina A
IA
Oldfield
Edward H
EH
Zhuang
Zhengping
Z
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009837:Oligodendroglioma / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000235:genetics*; D040901:Proteomics
D009363:Neoplasm Proteins; D020543:Proteome