N-myc oncogene expression and amplification in metastatic lesions of stage IV-S neuroblastoma

Abstract

The authors determined the levels of N-myc oncogene amplification and RNA expression in three infants with metastatic neuroblastoma. By clinical staging Patients 1 and 2 were Stage IV-S, a disease with limited metastatic potential and generally favorable outcome; Patient 3 was Stage IV. Southern blots of chromosomal DNA showed normal N-myc copy number in the primary tumor of Patient 1, extensive (200-fold) gene amplification in the primary tumor from Patient 2, and intermediate (100-fold) gene amplification in the primary tumor and metastatic lesions from Patient 3. N-myc RNA was expressed in all of the primary and metastatic tumor tissues tested. The level of N-myc RNA expression roughly corresponded to the extent of N-myc gene amplification in Patients 2 and 3 and was overexpressed from a single N-myc gene copy in Patient 1. N-myc gene amplification and RNA expression levels were approximately the same in the primary and metastatic lesions for each of the patients tested. The two patients with N-myc gene amplification had a poor outcome, but the patient with normal N-myc gene copy number had no evidence of disease. Despite the clinical picture in Patient 2 of Stage IV-S neuroblastoma, the pattern of N-myc amplification and expression more closely resembled that of Patient 3 (Stage IV neuroblastoma) than that of Patient 1 (bona fide Stage IV-S neuroblastoma).