Numerical and structural aberrations in advanced neuroblastoma tumours by CGH analysis; survival correlates with chromosome 17 status.
Rapid tumour progression in neuroblastoma is associated with MYCN amplification, deletion of the short arm of chromosome 1 and gain of 17q. However, patients with advanced disease without MYCN amplification and/or 1p deletion have a very poor outcome too, which suggests other genetic defects may predict an unfavourable prognosis. We employed CGH to study 22 tumours of patients at stages 3 and 4 over one year of age (6 and 16 cases respectively). Patients were divided in groups (A) long-term survivors and (B) short-term survivors. CGH showed a total of 226 chromosome imbalances (110 in group A and 116 in group B). The neuroblastoma cells of long-term survivors showed a preponderance of numerical aberrations (54%vs 43%); particularly gains of entire chromosomes 1 (P< 0.03), 7 (P< 0.04) and 19 (P< 0.05). An extra copy of 17 was detected in 6/8 (75%) samples of group A and only 1/14 (7%) samples of group B (P< 0.002). Conversely, tumours of patients who died from disease progression displayed a higher frequency of structural abnormalities (43%vs 35%), including loss of 1p, 9p, 11q, 15q and 18q and gain of 12q, although the difference was not significant (P = 0.24). Unbalanced gain of 17q was detected in 8/14 (57%) tumours of group B and only 1/8 (13%) tumours of group A (P< 0.05). The peculiar genetic difference observed in the tumours of long and short-term survivors may have prognostic relevance.
Cunsolo
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Solid Tumor Biology Unit, Advanced Biotechnology Center, National Institute for Cancer Research, Genoa, Italy.
Bicocchi
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MP
Petti
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Tonini
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D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019656:Loss of Heterozygosity; D008297:Male; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D009693:Nucleic Acid Hybridization; D011379:Prognosis; D016019:Survival Analysis