COMPARATIVE GENOMIC HYBRIDIZATION AND TELOMERASE ACTIVITY ANALYSIS IDENTIFY 2 BIOLOGICALLY DIFFERENT GROUPS OF 4S NEUROBLASTOMAS

Chromosomal aberrations of 20 stage 4s neuroblastomas were analysed by comparative genomic hybridization (CGH), In a subset of 13/20 tumours , telomerase activity was evaluated by the telomeric repeat amplificat ion protocol (TRAP). The CGH data were compared with the CGH results o f ten stage 1 and 2 (stage 1/2) and 22 stage 3 and 4 (stage 3/4) neuro blastomas. A total of 17/20 stage 4s neuroblastomas did not progress c linically, whereas tumour progression with lethal outcome occurred in 3/20 cases. The CGH data of clinically non-progressing stage 4s tumour s revealed a high rate of whole-chromosome aberrations (73.4%) with an overrepresentation of mainly chromosomes 2, 6, 7, 12, 13, 17, 18 and an underrepresentation of mainly chromosomes 3, 4, 11, 14. MYCN amplif ication or Ip deletion was observed in only 1/27 or 2/17 clinically no n-progressing stage 4s tumours respectively, whereas all three progres sive stage 4s neuroblastomas showed MYCN amplification, 1p deletion an d, in 2/3 cases, distal 17q gains. Except for one case, telomerase act ivity was not observed in non-progressing stage 4s neuroblastomas. In contrast, 4s tumours with lethal outcome revealed elevated telomerase activity levels. Our data suggest that stage 4s neuroblastomas belong to two biologically different groups, one of which displays the geneti c features of localized stage 112 tumours, whereas the other mimics ad vanced stage 3/4 neuroblastomas.