Mutations in the mitochondrial DNA D-Loop region occur frequently in adenocarcinoma in Barrett's esophagus
Mutations in the mitochondrial DNA D-Loop region occur frequently in adenocarcinoma in Barrett's esophagus
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DOI：
10.1038/sj.onc.1205532
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发表时间：
2002-05-23
期刊：
影响因子：
8
通讯作者：
Hoelscher, AH
中科院分区：
文献类型：
--
作者：
Miyazono, F;Schneider, PM;Hoelscher, AH
线粒体DNA（mtDNA）因缺乏保护性组蛋白、DNA修复系统效率低下以及持续暴露于氧自由基的诱变效应而导致高突变率。我们通过自动DNA测序检测了20例Barrett癌和相关Barrett上皮患者的mtDNA D-Loop区突变频率。在20例患者中的8例（40%）中检测到肿瘤和/或肿瘤相关Barrett上皮的突变。在8例阳性病例中，有6例仅在肿瘤中检测到突变，8例中有1例在肿瘤和巴雷特上皮中显示突变，8例中有1例仅在巴雷特上皮中检测到突变。Barrett上皮的异型增生程度在一个标本中被分类为低度，在两个标本中被分类为高度。mtDNA D-Loop突变与疾病的组织病理学分期或肿瘤分级无关。我们提出的第一个研究频繁发生突变的线粒体DNA D-环区在巴瑞特食管腺癌。此外，这项研究支持了氧化损伤可能是Barrett食管腺癌诱导机制的假设。由于突变是在肿瘤相关的发育异常的巴雷特上皮中发现的，它们也可能成为巴雷特上皮恶性潜能的标志物。
Mitochondrial DNA (mtDNA) is known for high mutation rates caused by lack of protective histones, inefficient DNA repair systems, and continuous exposure to mutagenic effects of oxygen radicals. We examined the frequency of mutations in the mtDNA D-Loop region in 20 patients with Barrett's carcinoma and associated Barrett's epithelium by automated DNA sequencing. Mutations were detected in eight of 20 (40%) patients in tumor and/or tumor-associated Barrett's epithelium. In six of eight positive cases, the mutations were detected only in the tumor, one of eight showed mutations in tumor and Barrett's epithelium, and one of eight only in Barrett's epithelium. The degree of dysplasia in Barrett's epithelium was classified low-grade in one and high grade in the two specimens. There was no association of mtDNA D-Loop mutations with histopathological stage of disease or tumor grading. We present the first study of frequent occurrence of mutations in the mtDNA D-Loop regions in adenocarcinomas in Barrett's esophagus. Furthermore, this study supports the hypothesis that oxidative damage might be a mechanism for the induction of adenocarcinoma in Barrett's esophagus. Since mutations were identified in tumor-associated dysplastic Barrett's epithelium, they also might become a marker for the malignant potential of Barrett's epithelium.