Mitochondrial DNA sequence variants in epithelial ovarian tumor subtypes and stages.
Mitochondrial DNA sequence variants in epithelial ovarian tumor subtypes and stages.
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DOI：
10.1186/1477-3163-6-1
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发表时间：
2007-01-26
影响因子：
--
通讯作者：
Partridge, Edward
中科院分区：
文献类型：
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作者：
Aikhionbare, Felix O;Mehrabi, Sharifeh;Kumaresan, K;Zavareh, Mojgan;Olatinwo, Moshood;Odunsi, Kunle;Partridge, Edward
大多数原发性卵巢肿瘤发生于卵巢上皮细胞表面。虽然高龄和阳性家族史是相关的危险因素，但上皮性卵巢肿瘤的病因尚不完全清楚。此外，知识的各种亚型的这种肿瘤的组织发生的因素，以及那些因素，促进卵巢恶性肿瘤的进展到晚期在很大程度上是未知的。目前的证据表明，参与细胞信号通路的线粒体改变可能与肿瘤发生有关。在这项研究中，我们确定了102例上皮性卵巢肿瘤中线粒体DNA（mtDNA）的多态性和其他序列变异的存在，其中包括10例与某些肿瘤配对的匹配正常组织。采用高分辨率限制性内切酶和PCR测序技术分析了3.3kb的mtDNA变异体，包括D-Loop和12 S rRNA-tRNAphe、tRNAval、tRNAser、tRNAasp、tRNAalys、ATPase 6、ATPase 8、细胞色素氧化酶I和II基因。共鉴定出352个mtDNA序列变异体，其中238个（68%）以前从未报道过。在IIIC期类胶质瘤中，12 S rRNA基因在np 772、773和780处有相对高的三个突变频率，其中两个是新的（773 delT和780 delC），并且以100%（7/7）的频率发生。此外，在浆液性肿瘤中仅观察到IV期的np 1657（10/10）和良性囊腺瘤（3/3）和交界性肿瘤（4/4）中的np 8221 delA突变。只有在浆液性亚型的早期阶段（良性囊腺瘤，3/3;交界性肿瘤，4/4; I期肿瘤，2/5和匹配的正常组织，4/4），才发现高频率，81%（13/16）的TC插入在np 310。我们的研究结果表明，某些mtDNA突变可以可靠地区分不同的组织学亚型的上皮性卵巢肿瘤。此外，这些数据提高了某些mtDNA突变可能是预测肿瘤侵袭性的有用生物标志物的可能性，并可能在肿瘤发生中发挥潜在作用。
A majority of primary ovarian neoplasms arise from cell surface epithelium of the ovaries. Although old age and a positive family history are associated risk factors, the etiology of the epithelial ovarian tumors is not completely understood. Additionally, knowledge of factors involved in the histogenesis of the various subtypes of this tumor as well as those factors that promote progression to advanced stages of ovarian malignancy are largely unknown. Current evidence suggests that mitochondrial alterations involved in cellular signaling pathways may be associated with tumorigenesis. In this study, we determined the presence of polymorphisms and other sequence variants of mitochondrial DNA (mtDNA) in 102 epithelial ovarian tumors including 10 matched normal tissues that paired with some of the tumors. High-resolution restriction endonucleases and PCR-based sequencing were used to assess the mtDNA variants spanning 3.3 kb fragment that comprised the D-Loop and 12S rRNA-tRNAphe, tRNAval, tRNAser, tRNAasp, tRNAlys, ATPase 6, ATPase 8, cytochrome oxidase I and II genes. Three hundred and fifty-two (352) mtDNA sequence variants were identified, of which 238 of 352 (68%) have not been previously reported. There were relatively high frequencies of three mutations in the 12S rRNA gene at np 772, 773, and 780 in stage IIIC endometrioid tumors, two of which are novel (773delT and 780delC), and occurred with a frequency of 100% (7/7). Furthermore, two mutations were observed in serous tumors only at np 1657 in stage IV (10/10), and at np 8221delA in benign cystadenomas (3/3) and borderline tumors (4/4). A high frequency, 81% (13/16) of TC insertion at np 310 was found only in early stages of serous subtype (benign cystadenomas, 3/3; borderline tumors, 4/4; stage I tumors, 2/5 and matched normal tissues 4/4). Our findings indicate that certain mtDNA mutations can reliably distinguish the different histologic subtypes of epithelial ovarian tumors. In addition, these data raise the possibility that certain mtDNA mutations may be useful biomarkers for predicting tumor aggressiveness and may play a potential role in tumorigenesis.