1q23 gain is associated with progressive neuroblastoma resistant to aggressive treatment

Neuroblastoma is one of the most common malignant tumors of childhood and i s characterized by regressive and progressive disease. Genetic factors that define progression of neuroblastomas ape still unknown. We performed compa rative genomic hybridization (CGH) on 27 neuroblastomas and dual-color fluo rescence in situ hybridization (FISH) to identify genetic aberrations assoc iated with progressive neuroblastoma showing resistance to aggressive treat ment. 17q21-q25 gains and MYCN amplification were associated with stage 4 n euroblastomas; however, these genetic aberrations had no significant relati on to the progression of stage 4 neuroblastomas. A novel chromosomal gain a t 1q21-q25 was found in 8 of 16 cases (50%) of stage 4 neuroblastoma. Gain of 1q21-q25 was observed in all of the progressive cases (8/8), which showe d resistance to chemotherapy, including 5 fatal neuroblastomas in stage 4, whereas 1q21-q25 gain was not found in any of the 8 remission cases in stag e 4. Survival analysis also showed that 1q21-q25 gain was associated with a poor outcome. High xenotransplantability in nude mice was observed for the tumors with 1q21-q25 gain (4/5; 80%). These data show that 1q21-q25 gain i s strongly associated with progression of stage 4 neuroblastoma. Furthermor e, by dual-color FISH analysis using cosmid clones, the 1q21-q25 gain was n arrowed to increase in DNA copy number on 1q23 in the fatal type of stage 4 neuroblastoma showing this gain. These results suggest that DNA amplificat ion at 1q23 may play a role in the development of progressive neuroblastoma in an advanced stage. (C) 1999 Wiley-Liss, Inc.