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Next generation RNA-sequencing in prognostic subsets of chronic lymphocytic leukemia

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Author

  • Larry Mansouri
  • Rebeqa Gunnarsson
  • Lesley-Ann Sutton
  • Adam Ameur
  • Sean D. Hooper
  • Markus Mayrhofer
  • Gunnar Juliusson
  • Anders Isaksson
  • Ulf Gyllensten
  • Richard Rosenquist

Summary, in English

Advances in next-generation RNA-sequencing have revealed the complexity of transcriptomes by allowing both coding and noncoding (nc) RNAs to be analyzed. However, limited data exist regarding the whole transcriptional landscape of chronic lymphocytic leukemia (CLL). In this pilot-study, we evaluated RNA-sequencing in CLL by comparing two subsets which carry almost identical or `` stereotyped'' B-cell receptors with distinct clinical outcome, that is the poor-prognostic subset # 1 (n = 4) and the more favorable-prognostic subset # 4 (n = 4). Our analysis revealed that 156 genes (e.g. LPL, WNT9A) and 76 ncRNAs, (e. g. SNORD48, SNORD115) were differentially expressed between the subsets. This technology also enabled us to identify numerous subset-specific splice variants (n = 406), which were predominantly expressed in subset # 1, including a splice-isoform of MSI2 with a novel start exon. A further important application of RNA-sequencing was for mutation detection and revealed 16-30 missense mutations per sample; notably many of these changes were found in genes with a strong potential for involvement in CLL pathogenesis, e. g., ATM and NOTCH2. This study not only demonstrates the effectiveness of RNA-sequencing for identifying mutations, quantifying gene expression and detecting splicing events, but also highlights the potential such global approaches have to significantly advance our understanding of the molecular mechanisms behind CLL development.

Department/s

Publishing year

2012

Language

English

Pages

737-740

Publication/Series

American Journal of Hematology

Volume

87

Issue

7

Document type

Journal article (letter)

Publisher

John Wiley & Sons Inc.

Topic

  • Hematology

Status

Published

ISBN/ISSN/Other

  • ISSN: 0361-8609