Purpose: The DNA repair enzyme O 6 -methylguanine DNA methyltransferase (MGMT) inhibits the killing of tumor cells by alkylating agents, and its loss in cancer cells is associated with hypermethylation of the MGMT CpG island. Thus, methylation of MGMT has been correlated with the clinical response to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in primary gliomas. Here, we investigate whether the presence of MGMT methylation in gliomas is also a good predictor of response to another emergent alkylating agent, temozolomide.Experimental Design: Using a methylation-specific PCR approach, we assessed the methylation status of the CpG island of MGMT in 92 glioma patients who received temozolomide as first-line chemotherapy or as treatment for relapses.Results

Recent studies have implicated simian virus 40 (SV40) in non-Hodgkin's lymphomas based on detection of SV40 DNA sequences. We employed a virus-like-particle (VLP)-based enzyme immunoassay for antibodies to SV40 to test sera from 520 lymphoma cases and 587 controls in Spain. The SV40 seroprevalence was 9.5% in controls and 5.9% in cases. Antibody levels of the positive sera were low. There was no association of SV40 seropositivity with any subtype of lymphoma. VLPs of the human BK virus substantially inhibited the SV40 reactivity of human sera. There was no serological evidence of widespread SV40 infection and no association of SV40 seropositivity with human lymphomas in Spain. © 2003 Wiley-Liss, Inc. Recent reports of the detection of simian virus 40 (SV40) DNA sequences in non-Hodgkin's lymphomas 1,2 add to a growing list of human cancers that may be associated with SV40 DNA positivity. 3 SV40 is a natural infection of Asiatic macaques to which millions of people were inadvertently exposed through contaminated poliovirus vaccines administered between 1955 and 1963. These vaccines were used in Spain but not applied universally. 4 Furthermore, the detection of SV40 in cancers in persons born after 1963 suggests that the virus may have established itself in human populations and is transmitted by person-to-person spread. Previous reports have largely relied on detection of viral DNA as evidence of SV40 infection. If SV40 circulates in human populations and is implicated in lymphomas, one might expect to detect serum antibodies to SV40 in lymphoma cases. We have employed a newly developed enzyme immunoassay (EIA) for SV40 antibodies 5 in a seroepidemiological study to evaluate the association between SV40 infection and lymphomas.Study subjects were recruited at 4 centers in Spain: Barcelona, Tortosa, Reus and Madrid. Cases were consecutive patients newly diagnosed with a lymphoid malignancy between 1998 and 2002. The diagnosis of lymphoma was verified by histology or cytopathology. Cases were categorized according to WHO Classification for Neoplastic Diseases of the Lymphoid Tissues. Controls were hospitalized patients matched to the cases by 5-year age group, gender and study center. Interviews were conducted to collect data on demographic, medical and family history, and environmental exposures. Cases and controls provided a blood sample. Informed consent was obtained from all subjects and the Institutional Review Boards of the participating centers approved the study.Of 703 eligible cases, 520 (74.0%) were included in the seroepidemiological study. Reasons for exclusion were refusal to participate (n ϭ 28), death before the interview (n ϭ 25), absence of blood sample (n ϭ 125) and absence of interview (n ϭ 5). Of 655 eligible controls, 587 (89.6%) were included in the study. Reasons for exclusion were refusal to participate (n ϭ 23) and absence of a blood sample (n ϭ 45).A recombinant baculovirus expressing VP1, the major capsid protein of SV40, was constructed and insect cells were infected with the virus. V...

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