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

Mansouri, Larry; Gunnarsson, Rebeqa; Sutton, Lesley-Ann; Ameur, Adam; Hooper, Sean D.; Mayrhofer, Markus; Juliusson, Gunnar LU ; Isaksson, Anders; Gyllensten, Ulf and Rosenquist, Richard (2012) In American Journal of Hematology 87(7). p.737-740
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Hematology
volume
87
issue
7
pages
737 - 740
publisher
John Wiley & Sons
external identifiers
  • wos:000305209700025
  • scopus:84862518030
ISSN
0361-8609
DOI
10.1002/ajh.23227
language
English
LU publication?
yes
id
499ed382-1395-4944-ba30-e9d008fc7500 (old id 2891026)
date added to LUP
2012-08-01 08:54:25
date last changed
2017-01-01 03:29:10
@article{499ed382-1395-4944-ba30-e9d008fc7500,
  abstract     = {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.},
  author       = {Mansouri, Larry and Gunnarsson, Rebeqa and Sutton, Lesley-Ann and Ameur, Adam and Hooper, Sean D. and Mayrhofer, Markus and Juliusson, Gunnar and Isaksson, Anders and Gyllensten, Ulf and Rosenquist, Richard},
  issn         = {0361-8609},
  language     = {eng},
  number       = {7},
  pages        = {737--740},
  publisher    = {John Wiley & Sons},
  series       = {American Journal of Hematology},
  title        = {Next generation RNA-sequencing in prognostic subsets of chronic lymphocytic leukemia},
  url          = {http://dx.doi.org/10.1002/ajh.23227},
  volume       = {87},
  year         = {2012},
}