Frequent Loss of Heterozygosity of a DNA Repair Gene, hOGG1, in Arteriovenous Malformation
MR Lindberg, H Zhang, LM Buckmiller, JY Suen, C-Y Fan. University of Arkansas for Medical Sciences, Little Rock, AR; John L. McClellan Memorial Veterans Hospital, Little Rock, AR
Background: Arteriovenous malformation (AVM) is a vascular anomaly that frequently occurs in the head and neck region. Most AVMs are diagnosed at birth and expand slowly with growth acceleration when changes in hormonal levels occur, such as at puberty, during pregnancy, or with use of birth control pills. While AVM is considered a benign lesion from a morphological point of view, it usually behaves aggressively with frequent recurrences. On the other hand, a small subset of AVMs is diagnosed in late adulthood and these tend to grow focally. In this study, we attempt to characterize the pattern of hOGG1 gene loss in relation to the biologic behavior of AVM.
Design: Seven lesions from 2 patients with aggressive AVM and 4 lesions from 3 patients with focal AVM were included in this study. A total of 11 sections from AVM and 11 from matched squamous epithelia in the same patients were used for microdissection of tissue. DNA samples were then obtained from dissected tissue and subjected to PCR amplification using 4 fluorescent-labeled microsatellite markers (D3S1289, D3S1297, D3S1300 and D3S1274), followed by fragment analysis using ABI PRISM 3100 Genetic Analyzer.
Results: All 7 lesions of aggressive AVM are informative with at least one of 4 markers used. Among these 7 lesions, 4 (57%) showed evidence of loss of heterozygosity (LOH). Three of 4 lesions of focal AVM are informative with at least one marker and 3 (66%) showed evidence of LOH. In one patient with aggressive AVM, one original AVM, two local recurrences (left face), and one geographically separate AVM (top of scalp) were analyzed. All 4 lesions showed an almost identical LOH pattern except that the 2nd left face recurrence and the scalp AVM contained an additional LOH at marker D3S1289. In this patient, the scalp AVM is completely separate from the left face AVM, which may represent a de novo second primary AVM or a metastasis from a subclone of the original AVM on the left face that has accumulated additional gene loss.
Conclusions: Loss of heterozygosity (gene loss) of the hOGG1 gene frequently occurs in AVM and the frequency of hOGG1 LOH does not differ significantly between aggressive and focal AVM. Accumulation of LOH at hOGG1 gene locus may be related to more aggressive growth of AVM.
Category: Head & Neck
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 171, Monday Morning