GENETIC CLINICAL MARKERS OF HUMAN NEUROBLASTOMA WITH SPECIAL REFERENCE TO N-MYCONCOGENE - AMPLIFIED OR NOT AMPLIFIED - AN OVERVIEW

Neuroblastoma is the most common extracranial tumor in children, and c ytogenetically, chromosome 1p deletions, extrachromosomal double minut es, and homogeneously staining regions (HSRs) are commonly observed in cell lines and in tumors in advanced stages. It is found that an HSR represents genomic amplification of N-myc, which plays a key role in d etermining the aggressiveness of neuroblastoma. However, stage IV neur oblastomas or cell lines which lack N-myc amplification are also progr essive, and some of them show evidence of N-myc expression in terms of mRNA and/or N-Myc oncoprotein. It was recently shown that a small pro ximal locus mapped between 1p35-36.1 and 1p36.23 may function as a sup pressor gene of N-myc amplification. In neuroblastoma, a pattern of di ploidy is associated with rapid tumor growth and poor survival. Expres sion of bc1-2 proto-oncogene is strongly associated with unfavorable h istology, while expressions of Ha-ras and trk-A proto-oncogenes indica te a favorable prognosis. trk-A proto-oncogene encodes a receptor for nerve growth factor. Genetic characteristics of neuroblastomas found b y urinary catecholamine mass screening are also discussed.