Integrated Epstein-Barr virus (EBV) and chromosomal abnormality in chronic active EBV infection

Abstract

In order to examine the role of Epstein-Barr virus (EBV) in the pathogenesis of chronic active EBV infection (CAEBV), we investigated whether or not EBV integration into the human genome is associated with any chromosonal abnormality. We therefore analyzed 4 cases of CAEBV: 2 cases showed a normal karyotype, while one had an oligo-clonal 6th chromo-somal abnormality and the fourth had a clonal 6th deletion (q15q23). In addition, the case with an oligo-clonal abnormality also had oligo-clonal EBV terminal repeat (TR) bands, while the case with a clonal abnormality showed a clonal TR band. In contrast, the 2 cases with a normal karyotype showed no clonal band. Two-color fluorescence in situ hybrid-ization (FISH) was used to detect the integrated EBV and the 6th chromosomal site. The presence of integrated EBV into the 6th chromosome was not frequent in the 2 cases with a normal karyotype, but it was statistically frequent in the case with an oligo-clonal 6th abnormality. In the case with a clonal 6th deletion, integration in the 6th chromosome was also slightly higher than that in the other chromosomes. In CAEBV, integrated EBV might thus be associated both with chromosomal abnormality and with pathogenesis. Int. J. Cancer 71:943-947, 1997. r 1997 Wiley-Liss, Inc.

Correlations between Epstein‐Barr virus and acute leukemia

“…Recent work using fluorescence in situ hybridization (FISH) and molecular genetics techniques suggests that EBV infection contributes to the genomic instability of BL and NPC . In addition, chromosome abnormalities have been observed in EBV‐associated HLH and CAEBV using FISH and cytogenetic analysis . Some subtypes of genetic changes may go undiagnosed using conventional cytogenetic analysis.…”

Epstein–Barr virus (EBV)‐positive pyothorax‐associated lymphoma (PAL): chromosomal integration of EBV in a novel CD2‐positive PAL B‐cell line

“…At present our data would not provide a direct evidence for a crucial role of integrated EBV in the neoplastic transformation of the cells, but following hypotheses could be considered. The viral integration itself may alter genetic stability of the cell genome (Popescu et al , 1993; Wolf et al , 1993; Jox et al , 1997; Ohshima et al , 1997). Although we currently do not know if the entire EBV genome was integrated in Pal‐1 cells, it would be expected that integration of several copies of the large EBV genome with the size of approximately 170 kb may well cause a chromosomal instability.…”

“…As a result, the marker chromosome was recognized as the site of EBV integration. Such structural alterations of the cell genomes may provide an advantage for malignant transformation (Wolf et al , 1993; Jox et al , 1997; Ohshima et al , 1997). Contribution of the viral integration event to the progression of cancers has been documented for other DNA viruses.…”

Proposed categorization of pathological states of EBV‐associated T/natural killer‐cell lymphoproliferative disorder (LPD) in children and young adults: Overlap with chronic active EBV infection and infantile fulminant EBV T‐LPD

“…Ohshima et al. observed a common chromosomal abnormality in the lymph nodes of patients with CAEBV, 30 and chromosomal alterations have been detected in peripheral blood mononuclear cells of 50% of a group of CAEBV patients 15 . The clonality of EBV‐infected cells has also been investigated using Southern blot hybridization with a probe targeting EBV terminal repeats 31 (CAEBV cases investigated by Ohshima.…”