Nikiforov Y E, Nikiforova M, Fagin J A
Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, Ohio 45267-0547, USA.
Oncogene. 1998 Oct 15;17(15):1983-8. doi: 10.1038/sj.onc.1202120.
Exposure to ionizing radiation induces different forms of genomic instability in cultured cells and experimental animals. A higher rate of germline mutations at human hypervariable minisatellite loci was reported in children born from parents exposed to radiation after Chernobyl, implicating genome destabilization as a possible mechanism responsible for late radiation effects in humans. To test if radiation-induced carcinogenesis in the thyroid gland may be associated with somatic minisatellite instability or microsatellite instability, we utilized a PCR-based approach to study normal and tumor DNA from 17 pediatric post-Chernobyl papillary thyroid carcinomas for mutations at three different minisatellite loci (D1S80, D17S30, ApoB), and 27 microsatellite loci of di-, tri-, or tetranucleotide repeats. Minisatellite instability was found in three (18%) tumors, with one of them exhibiting mutations in all three minisatellite loci, whereas two others showed mutations in one of two informative markers. By contrast, none of 20 sporadic thyroid cancers from patients with no history of radiation exposure was positive for minisatellite instability. Microsatellite analysis of post-Chernobyl tumors revealed a mutation in one (6%) tumor only at the locus of D10S1412, whereas all other 26 microsatellite markers showed identical patterns in each normal/tumor pair. Our results suggest that somatic cell microsatellite instability does not contribute to radiation-induced thyroid carcinogenesis. However, somatic minisatellite mutation events are present in a subset of radiation-induced, but not sporadic, thyroid cancers, suggesting that this type of genomic instability may play a role in radiation-induced tumorigenesis in the thyroid gland.
暴露于电离辐射会在培养细胞和实验动物中诱发不同形式的基因组不稳定。据报道，切尔诺贝利事故后受辐射的父母所生子女的人类高变微卫星位点的种系突变率更高，这意味着基因组不稳定可能是导致人类晚期辐射效应的一种机制。为了检验甲状腺辐射诱导的致癌作用是否可能与体细胞微卫星不稳定或微卫星不稳定有关，我们采用基于聚合酶链反应（PCR）的方法，研究了17例切尔诺贝利事故后的儿童乳头状甲状腺癌的正常和肿瘤DNA，检测三个不同微卫星位点（D1S80、D17S30、载脂蛋白B）以及27个二核苷酸、三核苷酸或四核苷酸重复的微卫星位点的突变情况。在三个（18%）肿瘤中发现了微卫星不稳定，其中一个在所有三个微卫星位点都有突变，而另外两个在两个信息性标记中的一个有突变。相比之下，20例无辐射暴露史患者的散发性甲状腺癌中没有一例微卫星不稳定呈阳性。对切尔诺贝利事故后肿瘤的微卫星分析显示，仅在一个（6%）肿瘤的D10S1412位点有突变，而其他所有26个微卫星标记在每对正常/肿瘤样本中都显示相同的模式。我们的结果表明，体细胞微卫星不稳定对辐射诱导的甲状腺致癌作用没有贡献。然而，体细胞微卫星突变事件存在于一部分辐射诱导而非散发性的甲状腺癌中，这表明这种类型的基因组不稳定可能在甲状腺辐射诱导的肿瘤发生中起作用。
