Tumour karyotype discriminates between good and bad prognostic outcome in neuroblastoma.
In 28 patients with neuroblastoma of different stages the karyotype was determined in the primary tumour and/or in the metastases by direct chromosome preparation or short term cell culture. In addition, DNA analysis for the proto-oncogene N-myc was performed for comparison in 10 cases. Abnormalities (deletions, translocations, derivations) of the short arm of chromosome 1 with the most frequent breakpoint at 1p32 (besides rarer aberrations in other chromosomes) were found in the tumour karyotype of 15 of 18 (83%) patients with metastatic disease (stage IV) and in 2 of 3 patients with stage III, but in none of the 7 patients with stages I, II, IV-S who are all alive with no evidence of disease. These 7 surviving patients with good prognosis had a hyperploid tumour karyotype, mainly in the triploid range. Eleven of the 18 (61%) patients with stage IV and 1 of 3 patients with stage III also contained double minutes (DMs) and/or homogeneously staining regions (HSRs) in their tumour karyotypes. N-myc amplification (30 to 60 copies) in the tumour DNA was detected in 2 of 6 (33%) examined cases with stage IV, in 1 out of 2 examined cases with stage III, and correlated with the presence of DMs/HSRs. Life table analysis showed a 90% probability of surviving in patients lacking the 1p abnormality as compared to less than 10% in patients with an aberrant 1p chromosome in the tumour cells. We conclude that tumour karyotype, in particular the structure of the short arm of chromosome 1, is the most important factor in determining the different outcome in children with neuroblastoma.
Christiansen
H
H
Kinderpoliklinik, Justus-Liebig-University, Giessen, West Germany.
Lampert
F
F
D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002878:Chromosomes, Human, Pair 1 / Q000648:ultrastructure; D004273:DNA, Neoplasm; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes
D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas