Epstein–Barr virus is integrated between REL and BCL-11A in American Burkitt lymphoma cell line (NAB-2)

Abstract

Epstein-Barr virus (EBV) initially isolated from the cultured Burkitt lymphoma (BL) cells, is one of the wellknown oncogenic virus. The NAB-2 line, which was established from a North American Burkitt's tumor, was indicated to contain one copy of EBV DNA as the integrated form into chromosome 2p13 of the host genome. To demonstrate the integration site of EBV directly, and to clarify the relation between the integration sites and the oncogenes, fragments containing the nucleotide sequence of NAB-2 integration sites were cloned. EBV was integrated via the terminal repeats (TR), and integration sites located in the clone RP11-440P5 on chromosome 2, between two oncogenes, REL and BCL11A, which is apart from approximately 350 kbp from each other. Expression level of REL in NAB-2 was increased. The flanking region of chromosome 2 at the bilateral junction sites showed no homology to the junction sites of EBV. The integration site 2p13 overlaps with common fragile site, FRA2E. NAB-2 cells expressed almost all latent genes but LMP-2A that flanks the TR, indicating the type III of latent infection of EBV. Integration event in NAB-2 might alter the regulation of the oncogenes and provide advantage for continuous cell proliferation.

Identifying candidate genes for 2p15p16.1 microdeletion syndrome using clinical, genomic, and functional analysis

“…Further evidence of genomic instability in the same region exists in cancer, leading to loss, gain, or amplification of 2p15p16.1 genes in approximately 30% of cases of lymphoma (53,54). It is interesting to note that cancer-related abnormalities in the 2p15p16.1 region were reported to coincide with fragile site, aphidicolin type, common, fra(2)(p13) (or FRA2E) (55).…”

Mutations in the NF-κB signaling pathway: implications for human disease

“…REL gene rearrangements have also been detected in two classical HL tumor samples: in one case, the REL gene is translocated to a position near the light chain enhancer and in the second case, there is an alteration near the 3 0 end of REL such that a C terminallytruncated REL protein is synthesized that shows constitutively nuclear staining . In addition, in one HL cell line, an Epstein-Barr virus genome has integrated near to REL, resulting in increased REL mRNA expression (Luo et al, 2004). Lastly, a Ser-to-Pro point mutation in the transactivation domain of REL (at Ser-525) has recently been detected in two human B-cell lymphomas (Starczynowski et al, 2006).…”

Gains of the proto-oncogene BCL11A and nuclear accumulation of BCL11AXL protein are frequent in primary mediastinal B-cell lymphoma

“…4 In the Burkitt's lymphoma cell line NAB-2, the EpsteinBarr virus (EBV) is integrated in the BCL11A locus leading to slightly higher BCL11A expression compared to other EBVpositive as well as EBV-negative Burkitt's lymphoma-derived cell lines. 5 Thus, deregulated expression of BCL11A through either genomic amplification, chromosomal translocation or abnormal activation (e.g., upon viral integration) is suggested to play a role in lymphomagenesis.…”