The recently identified epidemic of the acquired immunodeficiency syndrome (AIDS) is associated with a significant increase in the occurrence of some types of tumors, namely Kaposi's sarcoma and undifferentiated B cell lymphomas. We propose to investigate the genetic alterations which are involved in the pathogenesis of these two AIDS related neoplasias. Our studies will attempt to identify genetic alterations which are caused by viruses (DNA and RNA viruses) or by abnormal function of cellular oncogenes. The experimental plan will include analysis of both fresh tissues from patients and in vitro cell lines which we will attempt to establish as part of this project. In particular the following lines of research will be followed: 1) Kaposi's sarcoma. a) Attempt to establish cell lines by growing malignant endothelial cells which will be characterized for transformation parameters and compared to normal endothelial primary cultures. b) Analysis of cell lines and primary tumor cells for viral sequences, oncogene rearrangements and abnormal expression. c) Transfection of DNA from tumor cells into mouse NIH3T3 cells, and primary cultures of fibroblasts and endothelial cells in order to identify specific transforming sequences. 2) Undifferentiated B cell lymphomas. a) Lymphoblastoid cell lines can be developed with increased frequency from these patients. These lines appear to be not entirely similar to EBV transformed lymphoblastoid lines and will be studied as in 1) in order to determine whether they represent an early stage in the development of the tumor. b) Lymphoma cells will also be analyzed and cytogenetic abnormalities associated with c-myc oncogene activation will be compared with similar non-AIDS related lymphomas. c) Lymphoblastoid lines or tumor DNA will be transfected into NIH3T3 cells of lymphocytes. Alternatively tumor DNA will be tested on lymphoblastoid lines as recipients. These experiments will allow us to identify possible different oncogenes involved in different steps of malignant transformation.
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