[1908] Frequency of Loss of Heterozygosity (LOH) on Chromosome Arms 1p and 19q and Methylation of O-6-Methylguanine DNA Methyl Transferase (MGMT) Gene in Different Histologic Subtypes and Grades of Gliomas

G Sharma, A Raghunathan, M Cankovic, L Whiteley, JA Gutierrez, D Chitale. Henry Ford Hospital, Detroit, MI

Background: Loss of heterozygosity (LOH) 1p/19q has been associated with a better overall prognosis in oligodendroglial tumors, but its role in pure astrocytoma is far less important. Methylation of the DNA repair enzyme MGMT renders a subset of malignant gliomas sensitive to therapy with DNA alkylating agents. Molecular testing for LOH 1p19q and MGMT gene has been gradually but widely accepted in clinical practice. We sought to determine frequency of LOH 1p19q and MGMT methylation status (MGMT-M) among different types and grades of gliomas diagnosed and managed at our institution (a metropolitan tertiary care center) over last 3 years.
Design: Between January 2007 and April 2009, 130 cases of gliomas were tested for LOH 1p19q and MGMT-M. DNA was extracted using standard protocol from formalin fixed paraffin embedded tissues containing more than 80% of tumor. 1p19q allelic status was assessed by loss-of-heterozygosity assays in constitutional DNA/tumor DNA pairs by use of microsatellite markers. For MGMT promoter methylation, DNA was first treated with bisulfite followed by MethyLight assay utilizing TaqMan PCR principle.
Results: There were 65 astrocytomas (A) (1 grade1, 12 grade2, 18 grade3, 34 grade4/glioblastoma), 60 oligodendrogliomas (O) (33 grade2, 25 grade3, 2 grade4), 5 oligoastrocytomas (OA) (4 grade2, 1 grade3). Results for LOH 1p/19q and MGMT-M are as follows:

Table 1: Results for LOH 1p19q

Diagnosis	19q loss	1p loss	1p19q loss	Negative	Total
Astrocytoma	5 (7.6%)	10 (15.4%)	2 (3.1%)	48 (73.8%)	65
Oligodendroglioma	4 (6.7%)	3 (5%)	38 (63.3%)	15 (25%)	60
Oligoastrocytoma	1 (20%)	0	0	4 (80%)	5
Total	10 (7.7%)	13 (10%)	40 (30.7%)	67 (51.5%)	130

Table 2: Results for MGMT-M

Diagnosis	MGMT-M Negative	MGMT-M Positive	Total
Astrocytoma	37 (56.9%)	28 (43.1%)	65
Oligodendroglioma	19 (31.7%)	41 (68.3%)	60
Oligoastrocytoma	2 (40%)	3 (60%)	5
Total	58 (44.6%)	72 (55.4%)	130

Conclusions: Based on our series of 130 patients, we conclude that combined LOH 1p19q was significant in oligodendroglioma and was associated with frequent MGMT-M. Combined LOH1p19q was infrequent in astrocytomas and MGMT-M was frequently observed in 86% of high grade astrocytomas (43.1% overall). Oligodendroglial and astrocytic differentiations clearly have different molecular mechanisms and therapeutic targets.
Category: Pan-genomic/Pan-proteomic Approaches to Diseases

Monday, March 22, 2010 1:00 PM

Poster Session II # 236, Monday Afternoon