Copy Number and Gene Expression Alterations in Radiation-Induced Papillary Thyroid Carcinoma from Chernobyl Pediatric Patients
Copy Number and Gene Expression Alterations in Radiation-Induced Papillary Thyroid Carcinoma from Chernobyl Pediatric Patients
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DOI：
10.1089/thy.2009.0008
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发表时间：
2010-05-01
期刊：
影响因子：
6.6
通讯作者：
Hawthorn, Lesleyann
中科院分区：
文献类型：
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作者：
Stein, Leighton;Rothschild, Jenniffer;Hawthorn, Lesleyann
背景：在切尔诺贝利事故中暴露于辐射之后，事故发生时还是儿童的人的乳头状甲状腺癌(PTC)显著增加。我们使用了两个高通量的全基因组平台来分析切尔诺贝利地区儿童患者辐射诱导的PTC。方法：我们使用Affymetrix 50K图谱阵列对来自该地区的10个儿童切尔诺贝利后PTC进行比较基因组杂交和基因表达谱分析。我们对这两组数据进行了重叠分析。结果：检测到了许多拷贝数改变(CNA)的区域，包括从未与PTC相关的新区域。在染色体1p、5p、9q、12q、13q、16p、21q和22q上，拷贝数持续增加。缺失的观察频率较低，并被定位到1q、6q、9q、10q、13q、14q、21q和22q。基因表达分析表明，大多数改变的基因在散发性成人PTC中也存在扰动；然而，有141个基因表达变化是切尔诺贝利事件后肿瘤所独有的。在切尔诺贝利事故后的儿科肿瘤中，表达增加最多的新基因是TESC、PDZRN4、TraA/TRDa、GABBR2和CA12。降幅最大的基因包括PAPSS2、PDLIM3、Bexi、ANK2、SORBS2和PPARGCIA。然后进行基因表达和CNA图谱的重叠分析。这项分析确定了同时显示CNA和同时存在的基因表达变化的基因。其中许多常见于散发性PTC，如SERPINA、COL8A和PDX，而另一些则是辐射诱导的图谱所特有的，包括CAMK2N1、AK1、DHRS3和PDE9A。结论：这种类型的分析可以评估与物理机制相关的基因表达变化。这些基因和染色体区域是辐射诱导PTC的潜在标记。
Background: Following exposure to radiation during the Chernobyl fallout tragedy, papillary thyroid carcinoma (PTC) increased significantly in individuals who were children at the time of the accident. We have used two high-throughput, whole genome platforms to analyze radiation-induced PTCs from pediatric patients from the Chernobyl region.Methods: We performed comparative genomic hybridization using Affymetrix 50K Mapping arrays and gene expression profiling on 10 pediatric post-Chernobyl PTCs obtained from patients living in the region. We performed an overlay analysis of these two data sets.Results: Many regions of copy number alterations (CNAs) were detected including novel regions that had never been associated with PTCs. Increases in copy numbers were consistently found on chromosomes 1p, 5p, 9q, 12q, 13q, 16p, 21q, and 22q. Deletions were observed less frequently and were mapped to 1q, 6q, 9q, 10q, 13q, 14q, 21q, and 22q. Gene expression analysis revealed that most of the altered genes were also perturbed in sporadic adult PTC; however, 141 gene expression changes were found to be unique to the post-Chernobyl tumors. The genes with the highest increases in expression that were novel to the pediatric post-Chernobyl tumors were TESC, PDZRN4, TRAa/TRDa, GABBR2, and CA12. The genes showing the largest expression decreases included PAPSS2, PDLIM3, BEXI, ANK2, SORBS2, and PPARGCIA. An overlay analysis of the gene expression and CNA profiles was then performed. This analysis identified genes showing both CNAs and concurrent gene expression alterations. Many of these are commonly seen in sporadic PTC such as SERPINA, COL8A, and PDX, while others were unique to the radiation-induced profiles including CAMK2N1, AK1, DHRS3, and PDE9A.Conclusions: This type of analysis allows an assessment of gene expression changes that are associated with a physical mechanism. These genes and chromosomal regions are potential markers for radiation-induced PTC.