title: 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 as conventional and molecular cytogenetics may provide valuable clues for the identification of target loci and successful search for major genes in neuroblastoma. We aimed to investigate AURKA and MYCN gene rearrangements 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 also used on interphase nuclei to screen for alterations.
  
  
  RESULTS
  Some 18.4% of patient cells exhibited CAs., with a significant difference between patient and control groups in the frequencies (P<0.0001). Some 72% of the cells had structural aberrations, and only 28% had numerical chnages in patients. Structural aberrations consisted of deletions, translocations, breaks and fragility in various chromosomes, 84% and 52% of the patients having deletions 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 had chromosome breaks, most frequently in chromosomes 1, 2, 3, 4, 5, 8, 9, 11, 12, 19 and X. The number of cells with breaks 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.
  
  
  CONCLUSIONS
  Our data confirmed that there is a close correlation between amplification of the two genes, amplification of MYCN possibly contributing significantly to the oncogenic properties of AURKA. The high frequencies of chromosomal aberrations and amplifications of AURKA and MYCN genes indicate prognostic value in children with neuroblastomas and may point to contributing factors in their development.
authors: Department of Medical Biology and Genetics, Faculty of Medicine, Çukurova University, Adana, Turkey.
authors: Nihal
authors: N
authors: Inandiklioğlu
authors: Sema
authors: S
authors: Yilmaz
authors: Osman
authors: O
authors: Demirhan
authors: Seyda
authors: S
authors: Erdoğan
authors: Atila
authors: A
authors: Tanyeli
mesh_terms: D064096:Aurora Kinase A; D064127:Aurora Kinases; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D000071447:N-Myc Proto-Oncogene Protein; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases