Copy number increase of 1p36.33 and mitochondrial genome amplification in Epstein-Barr virus-transformed lymphoblastoid cell lines
Copy number increase of 1p36.33 and mitochondrial genome amplification in Epstein-Barr virus-transformed lymphoblastoid cell lines
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DOI：
10.1016/j.cancergencyto.2006.10.010
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发表时间：
2007-03-01
影响因子：
--
通讯作者：
Han, Bok-Ghee
中科院分区：
文献类型：
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作者：
Jeon, Jae-Pil;Shim, Sung-Mi;Han, Bok-Ghee
阵列CGH已被应用于检测癌症和遗传性疾病中的染色体畸变。EB病毒（EBV）感染的B淋巴细胞转化为持续增殖的淋巴母细胞样细胞系（LCL），其是用于人类遗传学研究的非常常见的基因组资源。我们使用细菌人工染色体（BAC）阵列CGH来评估EBV诱导的B细胞转化中LCL的染色体畸变。在早期传代时，与原代B细胞相比，LCL在1p36.33中表现出更大的拷贝数变异。定量聚合酶链反应（PCR）证实了1p36.33中拷贝数的增加。由于1p36.33的片段与线粒体DNA的一部分几乎相同，因此这种增加归因于线粒体DNA拷贝数的增加。LCL中线粒体生物发生相关基因的表达水平升高，这与线粒体DNA拷贝数增加一致，表明线粒体生物发生增加指示EBV介导的B细胞转化的进展。此外，我们的阵列CGH的LCL揭示了潜在的拷贝数多态性的染色体片段之间的韩国人口。总之，这些发现表明，早期传代中的LCL在EBV转化的B细胞永生化期间在细胞遗传学水平上保持了原代B细胞的染色体完整性，除了由于线粒体DNA拷贝数增加而导致的1 p36.33中的拷贝数变异。因此，对疾病的阵列CGH谱的分析应考虑1p36.33的拷贝数变异的可能性。(c)2007年爱思唯尔公司All rights reserved.
Array CGH has been applied to detect chromosomal aberrations in cancer and genetic diseases. Epstein-Barr virus (EBV)-infected B lymphocytes are transformed to continuously proliferating lymphoblastoid cell lines (LCLs), which are a very common genome resource for human genetic studies. We used bacterial artificial chromosome (BAC) array CGH to assess a chromosomal aberration of LCLs in EBV-induced B-cell transformation. At early passages, LCLs exhibited a greater copy number variation in 1p36.33 compared to primary B-cells. Quantitative polymerase chain reaction (PCR) confirmed the increase in the copy number in 1p36.33. Because a segment of 1 p36.33 is nearly identical to a part of the mitochondrial DNA, this increase was attributed to an increase in the copy number of mitochondrial DNA. The expression levels of mitochondrial biogenesis-related genes were elevated in the LCLs, which is consistent with the increased copy numbers of mitochondrial DNA, suggesting that increased mitochondrial biogenesis is indicative of the progression of EBV-mediated B-cell transformation. In addition, our array CGH of LCLs revealed potential copy number polymorphisms of chromosomal segments among Korean populations. Taken together, these findings suggest that LCLs in the early passages preserve the chromosomal integrity of primary B-cells at the cytogenetic level during EBV-transformed B-cell immortalization, except for a copy number variation in 1 p36.33 due to increased mitochondrial DNA copy numbers. Thus, analyses of array CGH profiles of diseases should take into account the potential for copy number variation of 1p36.33. (c) 2007 Elsevier Inc. All rights reserved.