HUMAN MESOTHELIOMAS CONTAIN THE SIMIAN-VIRUS-40 REGULATORY REGION ANDLARGE TUMOR-ANTIGEN DNA-SEQUENCES

Background: A cohort (20%) of patients with mesothelioma will not have an exposure to asbestos. Recently, a DNA tumor virus (simian virus 40 ) has been shown to cause hamster mesotheliomas; we previously describ ed simian virus 40-like DNA amino terminus sequences in 29 of 48 mesot heliomas. We analyzed an additional 42 mesotheliomas to determine (1) whether our initial observations were durable and (2) the extent to wh ich the simian virus 40 genome is present in mesotheliomas.,Methods: G enomic DNA was extracted from snap frozen mesothelioma tumor samples a nd from the simian virus 40-induced hamster mesothelioma tumor H9A, Po lymerase chain reaction primers were used to amplify various simian vi rus 40 large T-antigen regions including a 105-base pair amino terminu s fragment, a 281-base pair carboxyl terminus fragment, and a 310-base pair fragment of the enhancer promoter region. Endonuclease digestion s and Southern blotting were used to verify the expected product, Resu lts: Thirty of the 42 (71%) samples amplified T-antigen amino sequence s, and specificity was verified by Southern hybridization. Sixteen of 42 samples (38%) amplified the appropriate size fragment for the carbo xyl terminus, and digestion with BsaB1 matched that of H9A. Twenty-two of 42 samples (52%) amplified simian virus 40 regulatory sequences an d Fok1 digestion matched that of the hamster control tumor. Sequence a nalysis (4 patients) revealed 100% homology with the regulatory region of simian virus 40 strain 776, Conclusions: These data suggest an ass ociation between the simian virus 40 virus and human mesothelioma that could be exploited for diagnostic/therapeutic options including early detection and potential vaccination strategies.