Pashaei Shayesteh, Li Liwen, Zhang Haihong, Spencer Horace J, Schichman Steven A, Fan Chun-Yang, Smoller Bruce R
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
J Cutan Pathol. 2008 Jun;35(6):525-31. doi: 10.1111/j.1600-0560.2007.00865.x. Epub 2008 Feb 28.
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).
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.
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.
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.
皮肤黑色素瘤的一个主要风险因素是长期日晒和氧化应激。在各种氧化性DNA损伤中，8-氧代鸟嘌呤最为常见，如果修复不充分则可能具有致突变性。人类8-氧代鸟嘌呤DNA糖基化酶1（hOGG1）基因专门修复8-氧代鸟嘌呤，并且该基因在人类肿瘤中经常出现杂合性缺失（LOH）。在本研究中，我们调查hOGG1基因杂合性缺失是否发生在原位黑色素瘤（MIS）和相邻的非典型黑素细胞增生（AMH）中。
纳入12例含有MIS和相邻AMH的皮肤活检样本。从手动显微切割组织获得的DNA样本使用三种荧光标记的微卫星标记进行聚合酶链反应扩增，随后进行片段分析。
12例病例中有5例对于位于hOGG1基因座两侧的端粒（3S1297）和着丝粒（3S1289或3S1300）标记具有信息性。其中，4例（80%）MIS和3例（60%）AMH在两个标记处均显示hOGG1基因杂合性缺失。
这些结果表明hOGG1基因杂合性缺失与MIS和AMH相关，并提示hOGG1基因可能在黑素细胞肿瘤进展中起作用。
