Czarnecka Anna M, Klemba Aleksandra, Semczuk Andrzej, Plak Katarzyna, Marzec Barbara, Krawczyk Tomasz, Kofler Barbara, Golik Pawel, Bartnik Ewa
Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Pawinskiego 5a, 02-106, Warsaw, Poland.
School of Molecular Medicine, Medical University of Warsaw, Zwirki i Wigury 61, 02-091 Warsaw, Poland.
Int Arch Med. 2009 Oct 28;2(1):33. doi: 10.1186/1755-7682-2-33.
Endometrial carcinoma is the most commonly diagnosed gynaecological cancer in developed countries. Although the molecular genetics of this disease has been in the focus of many research laboratories for the last 20 years, relevant prognostic and diagnostic markers are still missing. At the same time mitochondrial DNA mutations have been reported in many types of cancer during the last two decades. It is therefore very likely that the mitochondrial genotype is one of the cancer susceptibility factors. To investigate the presence of mtDNA somatic mutations and distribution of inherited polymorphisms in endometrial adenocarcinoma patients we analyzed the D-loop sequence of cancer samples and their corresponding normal tissues and moreover performed mitochondrial haplogroup analysis. We detected 2 somatic mutation and increased incidence of mtDNA polymorphisms, in particular 16223C (80% patients, p = 0.005), 16126C (23%, p = 0.025) and 207A (19%, p = 0.027). Subsequent statistical analysis revealed that endometrial carcinoma population haplogroup distribution differs from the Polish population and that haplogroup H (with its defining polymorphism - C7028T) is strongly underrepresented (p = 0.003), therefore might be a cancer-protective factor. Our report supports the notion that mtDNA polymorphisms establish a specific genetic background for endometrial adenocarcinoma development and that mtDNA analysis may result in the development of new molecular tool for cancer detection.
子宫内膜癌是发达国家最常被诊断出的妇科癌症。尽管在过去20年里，该疾病的分子遗传学一直是许多研究实验室的重点，但相关的预后和诊断标志物仍然缺失。与此同时，在过去二十年中，许多类型的癌症都报告了线粒体DNA突变。因此，线粒体基因型很可能是癌症易感性因素之一。为了研究子宫内膜腺癌患者中线粒体DNA体细胞突变的存在情况以及遗传多态性的分布，我们分析了癌症样本及其相应正常组织的D环序列，此外还进行了线粒体单倍群分析。我们检测到2个体细胞突变以及线粒体DNA多态性的发生率增加，特别是16223C（80%的患者有此突变，p = 0.005）、16126C（23%，p = 0.025）和207A（19%，p = 0.027）。随后的统计分析表明，子宫内膜癌人群的单倍群分布与波兰人群不同，并且单倍群H（其特征性多态性为C7028T）的比例严重偏低（p = 0.003），因此可能是一种癌症保护因素。我们的报告支持这样一种观念，即线粒体DNA多态性为子宫内膜腺癌的发展建立了特定的遗传背景，并且线粒体DNA分析可能会促成用于癌症检测的新分子工具的开发。
