Concordant loss of heterozygosity of DNA repair gene, hOGG1, in melanoma in situ and atypical melanocytic hyperplasia.
BACKGROUND
One major risk factor for cutaneous melanoma is chronic sun-exposure and oxidative stress. Among various oxidative DNA damages, 8-oxoquanine is the most abundant and is potentially mutagenic if not sufficiently repaired. The human 8-oxoquanine DNA glycosylase 1 (hOGG1) gene specifically repairs 8-oxoguanine, and this gene shows frequent loss of heterozygosity (LOH) in human tumors. In this study, we investigate whether hOGG1 LOH occurs in melanoma in situ (MIS) and adjacent atypical melanocytic hyperplasia (AMH).


METHODS
Twelve skin biopsies with MIS and adjacent AMH were included. DNA samples derived from manual microdissection of tissues were subjected to polymerase chain reaction amplification using three fluorescent-labeled microsatellite makers, followed by fragment analysis.


RESULTS
Five of 12 cases were informative for both telomeric (3S1297) and centromeric (3S1289 or 3S1300) markers, bordering the hOGG1 locus. Among them, four (80%) MIS and three (60%) AMH showed hOGG1 LOH at both markers.


CONCLUSIONS
These results shows that LOH at hOGG1 gene is associated with MIS and AMH and suggest that the hOGG1 gene may play a role in melanocytic tumor progression.
Pashaei
Shayesteh
S
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Li
Liwen
L
Zhang
Haihong
H
Spencer
Horace J
HJ
Schichman
Steven A
SA
Fan
Chun-Yang
CY
Smoller
Bruce R
BR
D001706:Biopsy; D002503:Centromere / Q000235:genetics; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005819:Genetic Markers; D006801:Humans; D006965:Hyperplasia; D019656:Loss of Heterozygosity; D008544:Melanocytes / Q000473:pathology; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D016615:Telomere / Q000235:genetics
D004273:DNA, Neoplasm; D005819:Genetic Markers; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human