Chromosome Imbalances and Alterations of AURKA and MYCN Genes in Children with Neuroblastoma

Abstract

Background: Neuroblastoma (NB), like most human cancers, is characterized by genomic instability,manifested at the chromosomal level as allelic gain, loss or rearrangement. Genetics methods, as well asconventional and molecular cytogenetics may provide valuable clues for the identification of target loci andsuccessful search for major genes in neuroblastoma. We aimed to investigate AURKA and MYCN generearrangements and the chromosomal aberrations (CAs) to determine the prognosis of neuroblastoma.
Methods: We performed cytogenetic analysis by G-banding in 25 cases [11 girls (44%) and 14 boys (66%)]and in 25 controls. Fluorescence in situ hybridization (FISH) with AURKA and MYCN gene probes was alsoused on interphase nuclei to screen for alterations.
Results: Some 18.4% of patient cells exhibited CAs., with asignificant difference between patient and control groups in the frequencies (P<0.0001). Some 72% of the cellshad structural aberrations, and only 28% had numerical chnages in patients. Structural aberrations consistedof deletions, translocations, breaks and fragility in various chromosomes, 84% and 52% of the patients havingdeletions and translocations, respectively. Among these expressed CAs, there was a higher frequency at 1q21,1q32, 2q21, 2q31, 2p24, 4q31, 9q11, 9q22, 13q14, 14q11.2, 14q24, and 15q22 in patients. 32% of the patients hadchromosome breaks, most frequently in chromosomes 1, 2, 3, 4, 5, 8, 9, 11, 12, 19 and X. The number of cells withbreaks and the genomic damage frequencies were higher in patients (p<0.001). Aneuploidies in chromosomes X,22, 3, 17 and 18 were most frequently observed. Numerical chromosome abnormalities were distinctive in 10.7%of sex chromosomes. Fragile sites were observed in 16% of our patients.
Conclusion: Our data confirmed thatthere is a close correlation between amplification of the two genes, amplification of MYCN possibly contributingsignificantly to the oncogenic properties of AURKA. The high frequencies of chromosomal aberrations andamplifications of AURKA and MYCN genes indicate prognostic value in children with neuroblastomas and maypoint to contributing factors in their development.

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