Microarray comparative genomic hybridization reveals genome-wide patterns of DNA gains and losses in post-Chernobyl thyroid cancer
Microarray comparative genomic hybridization reveals genome-wide patterns of DNA gains and losses in post-Chernobyl thyroid cancer
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DOI：
10.1667/rr0547.1
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发表时间：
2006-09-01
影响因子：
3.4
通讯作者：
Neiman, Paul E.
中科院分区：
文献类型：
--
作者：
Kimmel, Robert R.;Zhao, Lue Ping;Neiman, Paul E.
电离辐射 DNA 链断裂导致的遗传增益和损失已在体外得到证实，并怀疑与辐射相关的甲状腺癌有关。我们假设，在与辐射暴露导致的假定 DNA 链断裂相关的肿瘤中，拷贝数偏差可能比自发的对应肿瘤更普遍，和/或以基因组模式出现。我们使用基于 cDNA 微阵列的比较基因组杂交技术，获得了 23 个切尔诺贝利事故后和 20 个自发性甲状腺癌中 14,573 个基因组位点的全基因组高分辨率拷贝数图谱。暴露个体的肿瘤中 DNA 增加的发生率比未暴露个体的病例高出两到四倍，而反复获得的子集则高出 10 倍。所有病例的 DNA 损失都很低，并且在自发病例中更为普遍。我们确定了依赖于辐射暴露史的独特的复制变异模式（主要是增益）。暴露的病例，尤其是年轻人，拥有更多的经常性增益，覆盖了更多的基因组。最大的区域跨度为 1.2 至 4.9 Mbp，位于 1p36.32-.33、2p23.2-.3、3p21.1-31、6p22.1-.2、7q36.1、8q24.3、9q34.11、9q34.3、11p15.5、 11q13.2-12.3、14q32.33、16p13.3、16p11.2、16q21-q12.2、17q25.1、19p13.31-qter、22q11.21 和 22q13.2。除了肿瘤形成过程之外，切尔诺贝利事故后甲状腺癌的拷贝数变化（尤其是增加）还受到辐射暴露和暴露年龄的影响。 (c) 2006 年，辐射研究协会。
Genetic gains and losses resulting from DNA strand breakage by ionizing radiation have been demonstrated in vitro and suspected in radiation-associated thyroid cancer. We hypothesized that copy number deviations might be more prevalent, and/or occur in genomic patterns, in tumors associated with presumptive DNA strand breakage from radiation exposure than in their spontaneous counterparts. We used cDNA microarray-based comparative genome hybridization to obtain genome-wide, high-resolution copy number profiles at 14,573 genomic loci in 23 post-Chernobyl and 20 spontaneous thyroid cancers. The prevalence of DNA gains in tumors from cases in exposed individuals was two- to fourfold higher than for cases in unexposed individuals and up to 10-fold higher for the subset of recurrent gains. DNA losses for all cases were low and more prevalent in spontaneous cases. We identified unique patterns of copy variation (mostly gains) that depended on a history of radiation exposure. Exposed cases, especially the young, harbored more recurrent gains that covered more of the genome. The largest regions, spanning 1.2 to 4.9 Mbp, were located at 1p36.32-.33, 2p23.2-.3, 3p21.1-31, 6p22.1-.2, 7q36.1, 8q24.3, 9q34.11, 9q34.3, 11p15.5, 11q13.2-12.3, 14q32.33, 16p13.3, 16p11.2, 16q21-q12.2, 17q25.1, 19p13.31-qter, 22q11.21 and 22q13.2. Copy number changes, particularly gains, in post-Chernobyl thyroid cancer are influenced by radiation exposure and age at exposure, in addition to the neoplastic process. (c) 2006 by Radiation Research Society.