Structural and functional analysis of cyclin-dependent kinase inhibitor genes (CDKN2A, CDKN2B, and CDKN2C) in neuroblastoma

Pediatric Research
A IolasconF D Ragione

Abstract

The status of the CDKN2A gene family, including CDKN2A, CDKN2B, and CDKN2C, was investigated in 24 cases of neuroblastoma. These genes were selected on the basis of 1) high incidence of their inactivation in several human cancers and 2) their localization on chromosomal regions (9p and 1p) frequently rearranged in neuroblastomas. Detailed molecular analyses indicated the absence of homozygous deletions and point mutations involving these genes in all investigated tumor samples. However, when loss of heterozygostity for chromosome 9p21 (the region where CDKN2A and CDKN2B are localized) was investigated, 16% of cases showed abnormalities in an area telomeric to the CDKN2A locus. To study transcriptional silencing of the CDKN2A gene, the methylation status of exon 1 was examined. In about 35% of cases, a partial methylation was evidenced. Analysis of the CDKN2A mRNA expression, however, did not show any relationship between methylation status and gene transcription. Finally, expression of the CDKN2B gene was demonstrated in all stage IV neuroblastomas, whereas none of stage I tumors expressed this gene. This finding suggests the occurrence of a correlation between CDKN2B transcription and tumor phenotype.

References

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Citations

Jun 26, 2001·FEBS Letters·F Della RagioneV Zappia
Mar 4, 2003·Nature Reviews. Cancer·Garrett M Brodeur
Nov 2, 2004·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·C L BassiL G Tone
Feb 14, 2020·International Journal of Molecular Sciences·Emanuela StamponeAdriana Borriello
Sep 12, 2012·Brain Tumor Pathology·Robert StawskiPawel P Liberski
Dec 31, 2003·Gene·Max M van Noesel, Rogier Versteeg

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