Oncogenomics

Oncogene (2010) 29, 3583–3592; doi:10.1038/onc.2010.106; published online 12 April 2010

An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours

P Mestdagh1,11, E Fredlund1,2,3,11, F Pattyn1, A Rihani1, T Van Maerken1, J Vermeulen1, C Kumps1, B Menten1, K De Preter1, A Schramm4, J Schulte4, R Noguera5, G Schleiermacher6,7, I Janoueix-Lerosey7, G Laureys8, R Powel9, D Nittner10, J-C Marine10, M Ringnér2,3, F Speleman1 and J Vandesompele1

  1. 1Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
  2. 2Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
  3. 3CREATE Health, Strategic Centre for Translational Cancer Research, Lund University, Lund, Sweden
  4. 4University Hospital of Essen, Essen, Germany
  5. 5Medical School in Valencia, Valencia, Spain
  6. 6Department of Paediatric Oncology, Institut Curie, Paris, France
  7. 7INSERM U830, Institut Curie, Paris, France
  8. 8Department of Pediatric Oncology, Ghent University Hospital, Ghent, Belgium
  9. 9PrimerDesign, Southampton, UK
  10. 10Laboratory for Molecular Cancer Biology, VIB-UGent, Ghent, Belgium

Correspondence: Dr J Vandesompele, Center for Medical Genetics, Ghent University Hospital, MRB, De Pintelaan 185, Ghent, East-Flanders 9000, Belgium. E-mail: Joke.Vandesompele@UGent.be

11These authors contributed equally to this work.

Received 19 September 2009; Revised 11 January 2010; Accepted 4 March 2010; Published online 12 April 2010.

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Abstract

Different classes of non-coding RNAs, including microRNAs, have recently been implicated in the process of tumourigenesis. In this study, we examined the expression and putative functions of a novel class of non-coding RNAs known as transcribed ultraconserved regions (T-UCRs) in neuroblastoma. Genome-wide expression profiling revealed correlations between specific T-UCR expression levels and important clinicogenetic parameters such as MYCN amplification status. A functional genomics approach based on the integration of multi-level transcriptome data was adapted to gain insights into T-UCR functions. Assignments of T-UCRs to cellular processes such as TP53 response, differentiation and proliferation were verified using various cellular model systems. For the first time, our results define a T-UCR expression landscape in neuroblastoma and suggest widespread T-UCR involvement in diverse cellular processes that are deregulated in the process of tumourigenesis.

Keywords:

neuroblastoma; T-UCR; non-coding RNA