Comparative genomic hybridization and telomerase activity analysis identify two biologically different groups of 4s neuroblastomas

C Brinkschmidt, C Poremba, H Christiansen, R Simon, K L Schäfer, H J Terpe, F Lampert, W Boecker, B Dockhorn-Dworniczak, C Brinkschmidt, C Poremba, H Christiansen, R Simon, K L Schäfer, H J Terpe, F Lampert, W Boecker, B Dockhorn-Dworniczak

Abstract

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 amplification protocol (TRAP). The CGH data were compared with the CGH results of ten stage 1 and 2 (stage 1/2) and 22 stage 3 and 4 (stage 3/4) neuroblastomas. A total of 17/20 stage 4s neuroblastomas did not progress clinically, whereas tumour progression with lethal outcome occurred in 3/20 cases. The CGH data of clinically non-progressing stage 4s tumours 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 amplification or 1p deletion was observed in only 1/27 or 2/17 clinically non-progressing stage 4s tumours respectively, whereas all three progressive stage 4s neuroblastomas showed MYCN amplification, 1p deletion and, in 2/3 cases, distal 17q gains. Except for one case, telomerase activity 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 genetic features of localized stage 1/2 tumours, whereas the other mimics advanced stage 3/4 neuroblastomas.

References

    1. Lancet. 1971 May 22;1(7708):1046-9
    1. N Engl J Med. 1983 Oct 20;309(16):989
    1. N Engl J Med. 1985 Oct 31;313(18):1111-6
    1. Am J Pediatr Hematol Oncol. 1987 Spring;9(1):8-10
    1. Br J Cancer. 1988 Jan;57(1):121-6
    1. Med Pediatr Oncol. 1989;17(2):111-5
    1. Cancer. 1990 May 1;65(9):1960-7
    1. J Clin Oncol. 1991 Apr;9(4):581-91
    1. J Clin Oncol. 1991 Aug;9(8):1371-5
    1. Med Pediatr Oncol. 1991;19(6):467-72
    1. Med Pediatr Oncol. 1991;19(6):473-7
    1. Science. 1992 Oct 30;258(5083):818-21
    1. Hum Genet. 1993 Feb;90(6):590-610
    1. J Clin Oncol. 1993 Aug;11(8):1466-77
    1. Genes Chromosomes Cancer. 1994 Aug;10(4):231-43
    1. Med Pediatr Oncol. 1995 Apr;24(4):215-21
    1. Cytometry. 1995 Jan 1;19(1):27-41
    1. Nat Med. 1995 Mar;1(3):249-55
    1. Eur J Cancer. 1995;31A(4):510-5
    1. N Engl J Med. 1996 Jan 25;334(4):225-30
    1. Oncol Res. 1995;7(3-4):121-30
    1. N Engl J Med. 1996 Jun 6;334(23):1505-11
    1. Genes Chromosomes Cancer. 1996 Nov;17(3):156-65
    1. J Clin Oncol. 1997 Jan;15(1):85-93
    1. Am J Pathol. 1997 Jan;150(1):81-9
    1. Genes Chromosomes Cancer. 1997 Mar;18(3):162-9
    1. J Pathol. 1997 Apr;181(4):394-400
    1. Genes Chromosomes Cancer. 1997 Jul;19(3):176-84
    1. Cancer. 1971 Feb;27(2):374-8

Source: PubMed

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