Detailed cytogenetic banding analysis will be applied to a variety of human cancers to assess directly clonal karyotypic abnormalities. Sequential chromosome studies will be conducted using a new cytogenetic procedure which samples tumor cells grown in an in vitro bioassay capable of supporting colony formation from a wide variety of human cancers. Specific time points for sequential analysis will be: (1) at diagnosis (prior to therapy); (2) following cessation of therapy (if measurable residual disease); and (3) at relapse. Patients with solid tumors and malignant effusions from breast, ovary, and lung cancer or patients with neuroblastoma will be studied. The objectives are to assess the clonal karyotypic evolution in primary and metastatic lesions as a response to time and treatment. Additionally, the karyology of tumor colony-forming cells exposed but resistant to in vitro incubation with various chemotherapeutic agents will be compared to unexposed control cultures. Selective action of these drugs on karyotypic clonal expansion or contraction will be assessed and results compared to measurable in vivo selection at the time of recurrence of disease. Finally, specific molecular probes for subsegments of chromosomal DNA will be employed to cytogenetically characterize further clonogenic tumor cells. Emphasis will be directed toward human oncogenic sequences, which will be mapped in normal and malignant cells to identify their chromosomal domain. (K)
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