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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Gain of chromosome band 7q11 in papillary thyroid carcinomas of young patients is associated with exposure to low-dose irradiation
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Gain of chromosome band 7q11 in papillary thyroid carcinomas of young patients is associated with exposure to low-dose irradiation

机译：年轻患者甲状腺甲状腺乳头状癌7q11染色体带的获得与低剂量照射有关

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摘要

The main consequence of the Chernobyl accident has been an increase in papillary thyroid carcinomas (PTCs) in those exposed to radioactive fallout as young children. Our aim was to identify genomic alterations that are associated with exposure to radiation. We used array comparative genomic hybridization to analyze a main (n = 52) and a validation cohort (n = 28) of PTC from patients aged <25 y at operation and matched for age at diagnosis and residency. Both cohorts consisted of patients exposed and not exposed to radioiodine fallout. The study showed association of a gain on chromosome 7 (7q11.22-11.23) with exposure (false discovery rate = 0.035). Thirty-nine percent of the exposed group showed the alteration; however, it was not found in a single case from the unexposed group. This was confirmed in the validation set. Because only a subgroup of cases in the exposed groups showed gain of 7q11.22-11.23, it is likely that different molecular subgroups and routes of radiation-induced carcinogenesis exist. The candidate gene CLIP2 was specifically overexpressed in the exposed cases. In addition, the expression of the genes PMS2L11, PMS2L3, and STAG3L3 correlated with gain of 7q11.22-11.23. An enrichment of Gene Ontology terms "DNA repair (PMS2L3, PMS2L5), "response to DNA damage stimulus" (BAZ1B, PMS2L3, PMS2L5, RFC2), and "cell-cell adhesion" (CLDN3, CLDN4) was found. This study, using matched exposed and unexposed cohorts, provides insights into the radiation-related carcinogenesis of young-onset PTC and, with the exposure-specific gain of 7q11 and overexpression of the CLIP2 gene, radiation-specific molecular markers.
机译：切尔诺贝利事故的主要后果是，年幼时暴露于放射性尘埃的甲状腺乳头状甲状腺癌（PTC）增多。我们的目的是确定与暴露于辐射有关的基因组改变。我们使用阵列比较基因组杂交技术分析了来自手术年龄<25岁且在诊断和住院年龄方面相匹配的患者的主要（n = 52）和验证队列（n = 28）。两组均包括暴露于放射性碘和未暴露于放射性碘的患者。研究显示，第7号染色体上的增益（7q11.22-11.23）与暴露相关（错误发现率= 0.035）。暴露组中有39％出现了改变；但是，在未曝光组的单个案例中都没有发现。这已在验证集中确认。因为暴露组中只有一小组病例显示出7q11.22-11.23，所以可能存在不同的分子亚组和放射致癌的途径。候选基因CLIP2在暴露的病例中特异性过表达。此外，基因PMS2L11，PMS2L3和STAG3L3的表达与7q11.22-11.23的增益相关。发现了丰富的基因本体术语，包括“ DNA修复（PMS2L3，PMS2L5），“对DNA损伤刺激的响应”（BAZ1B，PMS2L3，PMS2L5，RFC2）和“细胞间粘附”（CLDN3，CLDN4）。使用相匹配的暴露和未暴露队列，可以洞悉年轻发作PTC的辐射相关致癌作用，以及辐射特异性获得的7q11和CLIP2基因的过度表达以及辐射特异性分子标记。

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  • 作者

    Julia He(ss); Gerry Thomas; Herbert Braselmann; Verena Bauer; Tatjana Bogdanova; Johannes Wienberg; Horst Zitzelsberger; Kristian Unger;

  • 作者单位

    Research Unit of Radiation Cytogenetics, Helmholtz Zentrum Munchen, German Research Center for Environmental Health GmbH, 85764 Neuherberg,Germany;

    Human Cancer Studies Group, Department of Surgery and Cancer, Hammersmith Hospital, London W12 OHS, United Kingdom;

    Research Unit of Radiation Cytogenetics, Helmholtz Zentrum Munchen, German Research Center for Environmental Health GmbH, 85764 Neuherberg,Germany;

    Research Unit of Radiation Cytogenetics, Helmholtz Zentrum Munchen, German Research Center for Environmental Health GmbH, 85764 Neuherberg,Germany;

    Institute of Endocrinology and Metabolism, Academy of Medical Sciences of the Ukraine, 254114 Kiev, Ukraine;

    Department Biologie II, Anthropologie und Humangenetik, Ludwig-Maximilians-University, 82152 Martinsried, Germany;

    Research Unit of Radiation Cytogenetics, Helmholtz Zentrum Munchen, German Research Center for Environmental Health GmbH, 85764 Neuherberg,Germany;

    Human Cancer Studies Group, Department of Surgery and Cancer, Hammersmith Hospital, London W12 OHS, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    FISH; post-Chernobyl;

    机译：鱼;后切尔诺贝利;

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