Type

Journal Article

Authors

Raymond L Stallings
Rogier Versteeg
Jan Koster
Leah Alcock
Karen M Watters
Kenneth Bryan
Sudipto Das
Patrick G Buckley

Subjects

Biochemistry

Topics
humans pharmacology epigenesis genetic dna methylation gene expression regulation neoplastic azacitidine drug effects genetics analogs derivatives genome gene dosage telomere pathology neuroblastoma polymerase chain reaction

Genome-wide DNA methylation analysis of neuroblastic tumors reveals clinically relevant epigenetic events and large-scale epigenomic alterations localized to telomeric regions. (2010)

Abstract The downregulation of specific genes through DNA hypermethylation is a major hallmark of cancer, although the extent and genomic distribution of hypermethylation occurring within cancer genomes is poorly understood. We report on the first genome-wide analysis of DNA methylation alterations in different neuroblastic tumor subtypes and cell lines, revealing higher order organization and clinically relevant alterations of the epigenome. The methylation status of 33,485 discrete loci representing all annotated CpG islands and RefSeq gene promoters was assessed in primary neuroblastic tumors and cell lines. A comparison of genes that were hypermethylated exclusively in the clinically favorable ganglioneuroma/ganglioneuroblastoma tumors revealed that nine genes were associated with poor clinical outcome when overexpressed in the unfavorable neuroblastoma (NB) tumors. Moreover, an integrated DNA methylation and copy number analysis identified 80 genes that were recurrently concomitantly deleted and hypermethylated in NB, with 37 reactivated by 5-aza-deoxycytidine. Lower expression of four of these genes was correlated with poor clinical outcome, further implicating their inactivation in aggressive disease pathogenesis. Analysis of genome-wide hypermethylation patterns revealed 70 recurrent large-scale blocks of contiguously hypermethylated promoters/CpG islands, up to 590 kb in length, with a distribution bias toward telomeric regions. Genome-wide hypermethylation events in neuroblastic tumors are extensive and frequently occur in large-scale blocks with a significant bias toward telomeric regions, indicating that some methylation alterations have occurred in a coordinated manner. Our results indicate that methylation contributes toward the clinicopathological features of neuroblastic tumors, revealing numerous genes associated with poor patient survival in NB.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Raymond L Stallings, Rogier Versteeg, Jan Koster, Leah Alcock, Karen M Watters, Kenneth Bryan, Sudipto Das, Patrick G Buckley

Experts in our system

1
Raymond L Stallings
Royal College of Surgeons in Ireland
Total Publications: 59
 
2
Kenneth Bryan
Royal College of Surgeons in Ireland
Total Publications: 36
 
3
Sudipto Das
Royal College of Surgeons in Ireland
Total Publications: 15