The recent application of the high-resolution banding technique to the study of ANLL chromosomes suggests that a much higher proportion of leukemias than the 50 to 60% recognized with conventional banding methods may carry chromosome abnormalities. We intend to investigate all newly diagnosed and previously untreated acute leukemia patients admitted to Memorial Hospital. Investigation will employ high-resolution banding methods in order to reevaluate relationships between chromosome change and tumor histology on the one hand and patient prognosis on the other. Results of recent cytogenetic and molecular genetic studies of neoplastic cells now enable the question of the significance of chromosome change to neoplastic development to be addressed more rigorously than has been possible in the past. Thus, in the case of immunoglobulin-producing human and murine B-cell tumors, cellular proliferation is associated with specific translocations which bring together chromosomal regions which may be involved with control of proliferation (presumptive onc genes) with those containing genes which encode function (immunoglobulin synthesis). Thus, a class of chromosome rearrangements may be visualized which brings together onc genes with either their promoters or determinants of target cell function leading to development of neoplasia. We intend to test these hypotheses by ascertaining the constitutive position of onc genes, first in chromosomes from normal cells (of the germ line), and then in those of tumor cells in order to evaluate the significance of chromosome change in relation to onc gene sites. Gene mapping will be performed by in situ hybridization to chromosomes of onc genes and their cellular homologues cloned in appropriate vectors and labeled with ?3?H using methods developed by us for this purpose. During the past year the germ-line positions of ten retrovirally related oncogenes have been determined. Fine mappings of chromosomes 11 P, which contains several disease-related genes including C-Ha-ras-1, have been completed. Cytogenetic analyses of 180 ALL tumors (one of the largest series available) also have been completed. (K)
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