This grant has two interrelated objectives. One goal is to study the expression of several oncogenes in the fetal development of the peripheral and central nervous systems of murine and human fetuses. Mouse and human embryonic tissues of different stages of development will be studied by in situ hybridization with labeled N-myc, fos, abl, src, and ras probes. This method allows evaluation of gene expression in individual cells not possible by blotting techniques, which is critical in the study of heterogeneous tissue and early embryos. The other goal is to examine the expression of these genes, in particular N-myc in primitive human neural neoplasms. Several of these tumors occur at an early age and have close cytologic resemblance to cells of the developing nervous system, e.g., neuroblastoma, retinoblastoma, and medulloblastoma. Neuroblastomas in particular will be studied using an adaptation of in situ hybridization on tumor tissue embedded in histologic paraffin blocks. A """"""""library"""""""" of such blocks taken at different times during the clinical course of a large series of patients is available, and the expression of oncogenes can be correlated with the degree of differentiation, responsiveness to treatment, and clinical outcome. These correlative studies will be supplemented by experiments with neuroblastoma tissue culture lines where differentiation will be modulated by the addition of retinoic acid and other agents and the degree of differentiation will be related to N-myc expression. The purpose of these studies is to gain insight into the role of cellular oncogenes in normal and abnormal (neoplastic) tissue development. The evaluation of the degree of gene expression in these neural neoplasms may help to predict the clinical course and responsiveness to treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022430-03
Application #
3404803
Study Section
Neurology C Study Section (NEUC)
Project Start
1985-07-01
Project End
1988-09-30
Budget Start
1987-07-01
Budget End
1988-09-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143