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.
| Grady, E F; Schwab, M; Rosenau, W (1987) Expression of N-myc and c-src during the development of fetal human brain. Cancer Res 47:2931-6 |
| Grady-Leopardi, E F; Schwab, M; Ablin, A R et al. (1986) Detection of N-myc oncogene expression in human neuroblastoma by in situ hybridization and blot analysis: relationship to clinical outcome. Cancer Res 46:3196-9 |
