The expression of genes during the development of a pluripotent or progenitor cell into a differentiated, mature cell can provide a context for the study of tumorigenic cells whose origin is derived from such progenitor cells. In certain hematopoietic or epithelial tumors, malignant gene expression correlates substantially with the expression observed during normal development of the tissue from which the tumor originates, Gordon et al., J. Cell Biol. 108: 1187 (1989); Godal et al., Adv. Cancer Res. 36: 211 (1982). In fact, many biological activities of progenitor cells, including cellular migration and tissue remodeling, resemble pathological activities of cancer cells, such as metastases and tumor invasion.
Neuroblastoma, a tumor of the adrenal gland which afflicts persons during early childhood, is another system in which tumor biology correlates with that of normal differentiation and morphogenesis of its progenitor cells (neuroblast). Neuroblastoma is an embryonal tumor that exhibits both undifferentiated and differentiated histopathology. The development of neuroblastoma tumors mimics stages identifiable during histogenesis of its tissue of origin, the adrenal medulla. Cooper et al., Cell Growth and Diff. 1: 149 (1989).
During the development of human adrenal medulla neuroblast into mature chromaffin cells, four individual genes are expressed in a sequential pattern. Once a neuroblast is induced to differentiate along a neuroendocrine pathway, the progressive stages of chromaffin maturation are marked by a temporal expression of genes denoted TH, CGA, pG2 and B2M (Cooper, supra. at page 153). Cooper identified that the pattern of gene expression of these four markers in neuroblastoma cells mimics that of normal adrenal neuroblast arrested during three different stages of development.
One of these marker genes, pG2, was identified first in pheochromocytoma, a tumor of the adult adrenal medulla (Helman et al., PNAS USA 84: 2336 (1987)). Helman reported that pG2 also is highly expressed normal human adrenal cells.
Helman isolated a full-length cDNA from a human adrenal cDNA library, and identified a corresponding pG2 protein containing 286 amino acids, having a predicted molecular weight of 30,600 daltons (Helman et al., Nucleic Acids Res. 18(3): 685 (1990)).
A gene having developmentally-regulated expression, paralleling that of pG2, would be useful for detecting pheochromocytoma or neuroblastoma by genetic methods, especially since pG2 expression is restricted to the adrenal gland in non-malignant tissues.