A possible contributory role of BK virus infection in neuroblastoma development

The tumor suppressor protein p53 is aberrantly localized to the cytoplasm o f neuroblastoma cells, compromising the suppressor function of this protein , Such tumors are experimentally induced in transgenic mice expressing the large tumor (T) antigen of polyomaviruses. The oncogenic mechanisms of T an tigen include complex formation with, and inactivation of, the tumor suppre ssor protein p53, Samples from 18 human neuroblastomas and five normal human adrenal glands w ere examined, BK virus DNA was detected in all neuroblastomas and none of f ive normal adrenal glands by PCR, Using DNA in situ hybridization, polyomav iral DNA was found in the tumor cells of 17 of 18 neuroblastomas, but in no ne of five adrenal medullas. Expression of the large T antigen was detected in the tumor cells of 16 of 18 neuroblastomas, but in none of the five adr enal medullas, BS double immunostaining BK virus T antigen and p53 was colo calized to the cytoplasm of the tumor cells, Immunoprecipitation revealed b inding between the two proteins. The presence and expression of BK virus in neuroblastomas, but not in norma l adrenal medulla, and colocalization and binding to p53, suggest that this virus may play a contributory role in the development of this neoplasm.