AEG-1 Gene Copy Number Alterations in Human Gliomas
Hope T Richard, Jason F Harrison, Gregory N Fuller, Paul B Fisher, Christine E Fuller. Virginia Commonwealth University, Richmond, VA; University of Texas-MD Anderson, Houston, TX
Background: Gliomas represent the most common primary brain tumors in all age groups. Over the past few decades, research has uncovered numerous molecular alterations and pathway dysregulations involved in gliomagenesis. Although many potential biomarkers have been identified, treatment options for gliomas are limited, and mortality remains unacceptably high. Astrocyte elevated gene-1 (AEG-1) is a transmembrane protein that modulates multiple signal transduction pathways. AEG-1 overexpression has been found in cell lines and patient-derived samples of various carcinomas, neuroblastoma, and melanoma; AEG-1 gene amplification has similarly been found in breast and liver carcinomas. High AEG-1 expression was found in >90% of brain tumors in a recent study, particularly malignant gliomas. The current study aims to determine the incidence of AEG-1 gene copy number alterations in a broad cohort of gliomas.
Design: We reviewed the histologic features of 190 gliomas from two institutions. Dual color fluorescence in situ hybridization (FISH) was performed on tissue microarrays containing tumor core samples. A locus-specific probe targeting AEG-1(8q22) was paired with control probe for the centromeric region of chromosome 8 (CEP8). Correlations were sought between pathologic parameters and gene copy number status. Low level gain was defined as an AEG-1/CEP8 ratio of 1.2-2.0, with gene amplification having a ratio >2.0.
Results: The cohort included 81 glioblastoma / gliosarcoma (G), 27 anaplastic astrocytoma (AA), 17 anaplastic oligodendroglioma, 14 anaplastic oligoastrocytoma, 2 grade II astrocytoma, 21 oligodendroglioma, 8 oligoastrocytoma, 2 pleomorphic xanthoastrocytoma, 16 pilocytic astrocytoma (PA), and 2 glioneuronal tumors. Overall, 21% of gliomas tested harbored AEG-1 copy number gains. Gains were more frequently encountered in oligoastrocytomas (31%), AA (37%), and G (19%), though 13% of oligodendrogliomas were similarly involved. The majority of copy number alterations were low level gains, though 8% represented AEG-1 amplifications; the later finding was limited to high grade astrocytomas (AA and G). Of note, 12.5% of PA had AEG-1 copy number gain, whereas all other low grade gliomas were negative.
Conclusions: AEG-1 gene copy number gains are present in a wide variety of infiltrative gliomas as well as PA. Further basic science and translational studies will be needed to clarify AEG-1's viability as a prognostic biomarker and/or therapeutic target in gliomas.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 249, Tuesday Afternoon