Allelic loss of chromosome 1 and additional chromosome 17 material are both unfavourable prognostic markers in neuroblastoma.
In neuroblastoma, N-myc amplification and loss of heterozygosity for the short arm of chromosome 1 (LOH 1p) are common genetic abnormalities. We have recently shown that the presence of additional material of the long arm of chromosome 17 (add.17q) also occurs relatively frequently. In the present study, we analyzed a series of 55 tumors for LOH 1p, N-myc amplification and add.17q, using Southern blot analysis with polymorphic DNA probes of pairs of tumor and constitutional DNA. We determined the correlation of these parameters with clinical variables, such as age, stage, serum lactate dehydrogenase (LDH) and ferritin and also with outcome. LOH 1p occurred in 20 out of 55 cases (36%) and was found more often in stage III/IV tumors and in the older age group, although both correlations were not statistically significant. N-myc amplification was only demonstrated in 12 tumors with concomitant LOH 1p and was not present in the 35 cases without LOH 1p. Add.17q was found in 20/53 (38%) informative cases. LOH 1p was shown to be the most significant predictor of a poor outcome (P < 0.00001), independent of age and stage. LOH 1p is also of prognostic value in those cases without N-myc amplification, indicating a stronger prognostic value for LOH 1p. Add.17q was also associated with an unfavourable prognosis, although this was less significantly then with LOH 1p (P = 0.00004).
Caron
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Department of Paediatric Oncology and Haematology, Emma Kinder Ziekenhuis/Academic Medical Centre, Amsterdam, The Netherlands.
D000483:Alleles; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D002886:Chromosomes, Human, Pair 17; D004273:DNA, Neoplasm / Q000032:analysis; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D007223:Infant; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D016019:Survival Analysis
D004273:DNA, Neoplasm; D005819:Genetic Markers