Integration of Epstein-Barr virus into chromosome 6q15 of Burkitt lymphoma cell line (Raji) induces loss of BACH2 expression.
Epstein-Barr virus (EBV) initially isolated from cultured Burkitt lymphoma (BL) cells, is a well-known oncogenic virus. The Raji cell line was established from BL tissue and used for research worldwide. Previous study showed that each Raji cell contains an average of 50-60 EBV genome equivalents, and a significant proportion of the EBV genome is linearly integrated into host genome through BamHI-W close to the BamHI-Y fragment. However, a definitive EBV integration site in the chromosome has not been identified as yet. In this study, direct evidence that EBV DNA is integrated into the host genome was provided through cloning of the fragments containing nucleotide sequence of Raji integration sites. Integrated EBV DNA consisted of the BamHI-W fragment at one end and BamHI-D fragment at another end. Both junction sites were highly guanine/cytosine-rich. The BamHI-W fragment and the adjacent part of chromosome 6 showed 70% homology, while no homology was found between the BamHI-D and adjacent host sequences. EBV was present at intron 1 of the BACH2 gene located on chromosome 6q15. BACH2 was not expressed in the Raji cell line. Because BACH2 is a putative tumor suppressor gene, loss of its expression through EBV integration might contribute to lymphomagenesis.
Department of Pathology, Osaka University Graduate School of Medicine, Yamada-oka, Suita, Osaka, Japan. takakuwa@molpath.med.osaka-u.ac
Tetsuya
T
Takakuwa
Wen-Juan
WJ
Luo
Maria Francisca
MF
Ham
Femiko
F
Sakane-Ishikawa
Naoki
N
Wada
Katsuyuki
K
Aozasa
D000818:Animals; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D015139:Blotting, Southern; D002051:Burkitt Lymphoma / Q000821:virology*; D045744:Cell Line, Tumor; D002884:Chromosomes, Human, Pair 15 / Q000821:virology*; D017931:DNA Primers; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008223:Lymphoma / Q000235:genetics; D008969:Molecular Sequence Data; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017385:Sequence Homology; D014157:Transcription Factors / Q000096:biosynthesis*; D016662:Virus Integration / Q000502:physiology*
C491123:BACH2 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D017931:DNA Primers; D014157:Transcription Factors