Prevalence of mitochondrial DNA mutations in radiation associated human thyroid tumors

对辐射诱发甲状腺癌的分子事件知之甚少。因此，阐明分子辐射特征是了解甲状腺癌发病机制的紧迫任务之一。在我们的项目调查中，我们评估了切尔诺贝利事故后和对照甲状腺乳头状癌（PTC）中线粒体DNA（mtDNA）的一般和突变状态，以确定mtDNA的特定改变是否与受影响人群中可能的辐射沉降有关。我们重点研究了PTCs中mtDNA相对含量、常见缺失（CD）和大规模缺失的发生率和水平，结果表明，PTCs中mtDNA相对含量的升高与患者居住地的放射性碘污染水平或临床病理特征无关。CD水平升高主要见于放射相关组的肿瘤组织中，但在散发性PTC中未发现，但与临床病理参数、放射性碘污染和相对mtDNA含量无相关性。线粒体DNA大规模缺失的数量在大多数肿瘤组织中增加，特别是在放射相关组中，并倾向于与PTC中放射性污染物的水平相关。最重要的是，在放射相关肿瘤中发现了大规模mtDNA缺失的存在和相对mtDNA含量之间的高度显著的正相关性，我们得出结论，相对mtDNA水平和mtDNA缺失数量的一致性增加可能是放射相关PTC所特有的，并且构成了放射相关甲状腺癌的独特分子特征。

Molecular events underlying radiation-induced thyroid cancer are poorly understood. Therefore, elucidation of the molecular radiation signatures is one of the urgent tasks to understand pathogenesis of thyroid cancer in exposed individuals. In our investigation within the project, we evaluated general and mutational status of mitochondrial DNA(mtDNA) in the series of post-Chernobyl and control thyroid papillary cancer(PTC) to determine whether specific alterations in mtDNA can be linked to possible radiation fallout in the affected population. We focused on relative mtDNA content, prevalence and level of common deletion(CD) and large scale deletions in mtDNA.Our data demonstrate that elevated relative mtDNA content can be found in tumor tissue in most of cases of PTCs without correlation with the level of radioiodine contamination of patients' residency or with clinicopathological characteristics. Elevated level of CD was predominantly found in tumor tissue of the radiation associated group but not in sporadic PTCs, however no correlation was noted with clinicopathological parameters, radioiodine contamination and relative mtDNA content. The quantity of large scale deletions in mtDNA was elevated in most rumor tissues especially in the radiation associated group and tended to correlate with the level of radiopollutant in PTC. Most importantly, a highly significant positive correlation between the presence of large scale mtDNA deletions and relative mtDNA content was found in radiation-associated tumors.We concluded that concordant increase of both relative mtDNA level and number of mtDNA deletions may be specific to radiation associated PTC and comprise a distinctive molecular feature of radiation-associated thyroid cancer.