The putative role of transforming viruses in childhood acute lymphoblastic leukemia.

Epidemiological evidence suggests that infection is involved in the etiology of common acute lymphoblastic leukemia, either by stimulating an inappropriate immune response or in the form of a classical transforming agent. In an attempt to elucidate the role that infection is playing in this disease, we used representational difference analysis (RDA) to examine tumor samples for the presence of exogenous genomes. Twenty RDA experiments were carried out, using four different restriction enzymes, but no exogenous sequences were identified within leukemic cells. These results suggest that it is unlikely that a single, direct transforming agent is involved in the pathogenesis of common acute lymphoblastic leukemia.

Association between simian virus 40 DNA and lymphoma in the United kingdom.

Recent studies have reported the presence of simian virus 40 (SV40) DNA sequences in approximately 40% of tumor samples from non-Hodgkin's lymphoma (NHL) patients from the United States. We examined a series of 259 tumor and blood samples, including 152 NHL samples, from patients in the U.K. with lymphadenopathy and lymphoid leukemia for the presence of SV40 DNA using a highly sensitive quantitative polymerase chain reaction (PCR) assay and a consensus PCR assay capable of detecting the polyomaviruses SV40, BK, and JC. SV40 DNA sequences were not detected in any sample using either assay. Because the incidence of NHL is similar in the U.K. and the United States, this finding suggests that SV40 is unlikely to have an etiologic role in NHL.

Viruses and Hodgkin disease: no evidence of novel herpesviruses in non-EBV-associated lesions.

The Epstein-Barr virus (EBV) is associated with a proportion of cases of Hodgkin disease (HD) and this association is believed to be causal. Epidemiological studies suggest that an infectious agent is involved in the aetiology of young adult HD, however, cases in this age group are less likely to have EBV-associated disease than cases diagnosed in early childhood or older adult years. Molecular studies have failed to find a consistent association between HD and other candidate viruses, and the aetiology of non-EBV-associated cases remains obscure. We looked for evidence of herpesvirus infection in samples of non-EBV-associated HD using a highly sensitive, degenerate PCR assay. Despite exhaustive sequence analysis of PCR products, no novel herpesviruses were identified. These results suggest that it is extremely unlikely that a novel herpesvirus is involved in the pathogenesis of non-EBV-associated HD.

Analysis of Epstein-Barr virus (EBV) nuclear antigen 1 subtypes in EBV-associated lymphomas from Brazil and the United Kingdom.

EBNA-1 is the only viral protein consistently expressed in all cells latently infected by Epstein-Barr virus (EBV). There is a high frequency of sequence variation within functionally important domains of EBNA-1, with five subtypes identified. Individuals may be infected with multiple EBV strains (classified according to EBNA-1 subtype), but Burkitt's lymphoma (BL) tumours carry a single subtype and exhibit some subtype preference. Subtype variation has also been related to geographical location. In the present study EBNA-1 polymorphisms were examined in a series of haematological malignancies from two distinct geographical regions, Brazil and the United Kingdom. Nucleotide sequence analysis of the carboxy-terminal region of EBNA-1 in 34 cases revealed six distinct sequences, some of which are novel. A new subtype, named V-Ala, was identified. EBNA-1 subtype in tumours differed markedly according to geographical location. In contrast to previous studies, we found evidence of EBNA-1 sequence variation within individual BL tumour samples.