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snoRNPs Regulate Telomerase Activity in Neuroblastoma and Are Associated with Poor Prognosis.

Author:
  • Kristoffer von Stedingk
  • Jan Koster
  • Marta Piqueras
  • Rosa Noguera
  • Samuel Navarro
  • Sven Påhlman
  • Rogier Versteeg
  • Ingrid Øra
  • David Gisselsson Nord
  • David Lindgren
  • Håkan Axelson
Publishing year: 2013
Language: English
Pages: 142-447
Publication/Series: Translational Oncology
Volume: 6
Issue: 4
Document type: Journal article
Publisher: Neoplasia Press

Abstract english

Amplification of the MYCN oncogene is strongly associated with poor prognosis in neuroblastoma (NB). In addition to MYCN amplification, many studies have focused on identifying patients with a poor prognosis based on gene expression profiling. The majority of prognostic signatures today are comprised of large gene lists limiting their clinical application. In addition, although of prognostic significance, most of these signatures fail to identify cellular processes that can explain their relation to prognosis. Here, we determined prognostically predictive genes in a data set containing 251 NBs. Gene Ontology analysis was performed on significant genes with a positive hazard ratio to search for cellular processes associated with poor prognosis. An enrichment in ribonucleoproteins (RNPs) was found. Genes involved in the stabilization and formation of the central small nucleolar RNP (snoRNP) complex were scrutinized using a backward conditional Cox regression resulting in an snoRNP signature consisting of three genes: DKC1, NHP2, and GAR1. The snoRNP signature significantly and independently predicted prognosis when compared to the established clinical risk factors. Association of snoRNP protein expression and prognosis was confirmed using tissue micro-arrays. Knockdown of snoRNP expression in NB cell lines resulted in reduced telomerase activity and an increase in anaphase bridge frequency. In addition, in patient material, expression of the snoRNP complex was significantly associated with telomerase activity, occurrence of segmental aberrations, and expression-based measurements of chromosomal instability. Together, these results underscore the prognostic value of snoRNP complex expression in NB and suggest a role for snoRNPs in telomere maintenance and genomic stability.

Keywords

  • Cancer and Oncology

Other

Published
  • Kidney cancer research group
  • ISSN: 1936-5233
Sven Påhlman
E-mail: sven [dot] pahlman [at] med [dot] lu [dot] se

Professor

Division of Translational Cancer Research

+46 46 222 64 21

MV406 312K1

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