Miyazono Futoshi, Schneider Paul M, Metzger Ralf, Warnecke-Eberz Ute, Baldus Stephan E, Dienes Hans P, Aikou Takashi, Hoelscher Arnulf H
Department of Visceral and Vascular Surgery, University of Cologne, Joseph-Stelzmann-Strasse 9, 50931 Cologne, Germany.
Oncogene. 2002 May 23;21(23):3780-3. doi: 10.1038/sj.onc.1205532.
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.
线粒体DNA（mtDNA）因其缺乏保护性组蛋白、DNA修复系统效率低下以及持续暴露于氧自由基的诱变作用而具有高突变率。我们通过自动DNA测序检查了20例巴雷特癌及相关巴雷特上皮患者线粒体DNA D环区域的突变频率。在20例患者中的8例（40%）肿瘤和/或肿瘤相关的巴雷特上皮中检测到突变。在8例阳性病例中的6例中，仅在肿瘤中检测到突变，8例中的1例在肿瘤和巴雷特上皮中显示突变，8例中的1例仅在巴雷特上皮中检测到突变。巴雷特上皮的发育异常程度在1个标本中分类为低级别，在2个标本中分类为高级别。mtDNA D环突变与疾病的组织病理学分期或肿瘤分级无关。我们首次对巴雷特食管腺癌中线粒体DNA D环区域频繁发生突变进行了研究。此外，本研究支持氧化损伤可能是巴雷特食管腺癌诱导机制的假说。由于在肿瘤相关的发育异常巴雷特上皮中发现了突变，它们也可能成为巴雷特上皮恶性潜能的标志物。
