title: Copy number increase of 1p36.33 and mitochondrial genome amplification in Epstein-Barr virus-transformed lymphoblastoid cell lines.
abstract: 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 1p36.33 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 1p36.33 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.
authors.affiliation: BioBank for Health Sciences, Center for Genome Science, National Institute of Health, Korea Center for Disease Control and Prevention, 5 Nokbun, Eunpyung-Gu, Seoul 122-701, Republic of Korea.
authors.forename: Jae-Pil
authors.initials: JP
authors.lastname: Jeon
authors.forename: Sung-Mi
authors.initials: SM
authors.lastname: Shim
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Nam
authors.forename: Seung-Youn
authors.initials: SY
authors.lastname: Baik
authors.forename: Jun-Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Bok-Ghee
authors.initials: BG
authors.lastname: Han
mesh_terms: D000782:Aneuploidy; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000235:genetics; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005784:Gene Amplification; D015870:Gene Expression; D015894:Genome, Human / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D046228:Microarray Analysis / Q000379:methods; D024101:Mitochondrial Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012333:RNA, Messenger