THE HPV-16 GENOME INDUCES CARCINOMAS AND T-CELL LYMPHOMAS IN TRANSGENIC MICE

Human papillomavirus type 16 is highly associated with cervical carcin oma. Here we report families of transgenic mice produced by the microi njection of a dimer repeat sequence of the human papillomavirus type 1 6 genome. Thirty-two transgenic animals in four families developed mul tiple organ malignancies that appeared in middle age without other int ervention. The tumor phenotype of poorly differentiated carcinomas or malignant lymphomas and the transgene cosegregate in these lineages Th e tumors arise in the subcutaneous compartment, thoracic cavity, or ab domen; are widely metastatic; and grow rapidly in nude mice No cervica l lesions were identified in six females examined. No rearrangements i n transgene E6/E7, E2, and E1 regions were found in tumor tissues, and the truncated E2 region, which was thought to play an important role in human cervical carcinogenesis, teas not needed for tumorigenesis in these animals. The transgenic mice produce RNA from the E6/E7 open re ading frames, which has been identified in both the carcinomas and the lymphomas, but RNA from the E2 open reading frame is present only itt malignant T-cell lymphomas and not in carcinomas, hyperplastic lympho id tissue, or normal lymphoid tissue.