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Håkan Axelson

Håkan Axelson

Research team manager

Håkan Axelson

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

Summary, in 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.

Department/s

  • Department of Translational Medicine
  • Paediatrics (Lund)
  • Division of Clinical Genetics
  • Kidney cancer research group
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2013

Language

English

Pages

447-457

Publication/Series

Translational Oncology

Volume

6

Issue

4

Document type

Journal article

Publisher

Neoplasia Press

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Kidney cancer research group

ISBN/ISSN/Other

  • ISSN: 1936-5233