Molecular markers of clonality and identity in Epstein-Barr virus-associated B-cell lymphoproliferative disease.
Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disease may be polyclonal, oligoclonal, or monoclonal. The degree of tumor clonality reflects the disease pathogenesis and may have implications for disease diagnosis, prognosis, and treatment. In this study, specimens of EBV-associated B-cell lymphoproliferative disease obtained from immunocompromised hosts were analyzed for molecular markers of cellular and virologic clonality and virologic identity. Each tumor specimen was assessed for immunoglobulin gene JH region rearrangement, the structure of the EBV genome termini, and the EBV genotype(s) present using a new EBV genotyping assay based upon LMP-1 gene sequence variation. The results of the JH rearrangement and EBV termini assays were generally concordant in their assessment of tumor specimen clonality, and both assays contributed to establishing clonal identity between different tumor specimens. The EBV genotyping assay did not significantly contribute to the assessment of tumor clonality but did established clear virologic identity between different tumor specimens obtained from the same individual. In one individual, these three assays together characterized a multi-focal, monoclonal tumor that may have arisen through clonal selection after sequential infections with two different EBV genotypes. In summary, the JH rearrangement and EBV termini assays each provided different but complementary information on tumor clonality, while the EBV genotyping assay proved most useful for establishing virologic identity among tumors. Utilization of these three assays together may provide new insight into the pathogenesis of EBV-associated B-cell lymphoproliferative disease.
Walling
Dennis M
DM
Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch at Galveston, 77555-0435, USA. dwalling@utmb.edu
Andritsos
Leslie A
LA
Etienne
Wiguins
W
Payne
Deborah A
DA
Aronson
Judith F
JF
Flaitz
Catherine M
CM
Nichols
C Mark
CM
D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D002999:Clone Cells; D020031:Epstein-Barr Virus Infections / Q000821:virology*; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D005814:Genes, Viral; D005819:Genetic Markers; D005838:Genotype; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007144:Immunoglobulin J-Chains / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000821:virology*; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017421:Sequence Analysis; D014763:Viral Matrix Proteins / Q000235:genetics
D014408:Biomarkers, Tumor; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D005819:Genetic Markers; D007143:Immunoglobulin Heavy Chains; D007144:Immunoglobulin J-Chains; D014763:Viral Matrix Proteins