Correlation between the number of segmental chromosome aberrations and the age at diagnosis of diploid neuroblastomas without MYCN amplification

Abstract

Background In neuroblastomas (NBs) without MYCN amplification, segmental chromosome aberrations SCAs such as 1p loss, 11q loss, and 17q gain have been suggested to be associated with the prognosis of the patients. We assessed the correlation between the number of SCAs and other biological factors in primary NBs samples. Method The status of SCAs in 54 primary NBs samples was analyzed using the single-nucleotide polymorphism (SNP) array (Human CMV370-Duo; Illumina, San Diego, CA). The status of MYCN amplification was determined by an SNP array and the fluorescence in situ hybridization method. The DNA ploidy was determined by flow cytometry. Results Nine of 54 samples showed MYCN amplification. All 9 samples with MYCN amplification and 20 of 45 samples without MYCN amplification showed diploidy/tetraploidy, and the other 25 samples without MYCN amplification showed aneuploidy. The most frequent SCAs were 17q gain (26/54; 48.1%) and 11q loss (16/54; 29.6%), followed by 1p loss (15/54; 27.8%). The number of SCAs in diploidy/tetraploidy NBs without MYCN amplification (7.00 ± 4.67) was higher than that in NBs with MYCN amplification (4.78 ± 2.82) and in aneuploid NBs (1.64 ± 2.78) ( P < .05). In diploid/tetraploid NBs without MYCN amplification, there was a significant difference between an age at diagnosis less than 12 months (n = 7) and over 12 months (n = 13) (4.14 ± 3.63 vs 8.54 ± 4.54; P = .04). Moreover, the number of SCAs correlated with the age at diagnosis in diploid/tetraploid samples without MYCN amplification ( r = 0.70, P = .0006). In NBs with MYCN amplification, the number of SCAs did not correlate with the age at diagnosis. Conclusion The number of SCAs significantly increased in proportion to age at diagnosis in diploid/tetraploid NBs without MYCN amplification. The increase in the number of these SCAs may play an important role in the prognosis of patients without MYCN amplification over 12 months of age.