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RNA sequencing of sarcomas with simple karyotypes: identification and enrichment of fusion transcripts.

Hofvander, Jakob LU ; Tayebwa, Johnbosco LU ; Nilsson, Jenny LU ; Magnusson, Linda LU ; Brosjö, Otte; Larsson, Olle; Vult von Steyern, Fredrik LU ; Domanski, Henryk LU ; Mandahl, Nils LU and Mertens, Fredrik LU (2015) In Laboratory Investigation 95(6). p.603-609
Abstract
Gene fusions are neoplasia-associated mutations arising from structural chromosomal rearrangements. They have a strong impact on tumor development and constitute important diagnostic markers. Malignant soft tissue tumors (sarcomas) constitute a heterogeneous group of neoplasms with >50 distinct subtypes, each of which is rare. In addition, there is considerable morphologic overlap between sarcomas and benign lesions. Several subtypes display distinct gene fusions, serving as excellent biomarkers. The development of methods for deep sequencing of the complete transcriptome (RNA-Seq) has substantially improved the possibilities for detecting gene fusions. With the aim of identifying new gene fusions of biological and clinical relevance,... (More)
Gene fusions are neoplasia-associated mutations arising from structural chromosomal rearrangements. They have a strong impact on tumor development and constitute important diagnostic markers. Malignant soft tissue tumors (sarcomas) constitute a heterogeneous group of neoplasms with >50 distinct subtypes, each of which is rare. In addition, there is considerable morphologic overlap between sarcomas and benign lesions. Several subtypes display distinct gene fusions, serving as excellent biomarkers. The development of methods for deep sequencing of the complete transcriptome (RNA-Seq) has substantially improved the possibilities for detecting gene fusions. With the aim of identifying new gene fusions of biological and clinical relevance, eight sarcomas with simple karyotypes, ie, only one or a few structural rearrangements, were subjected to massively parallel paired-end sequencing of mRNA. Three different algorithms were used to identify fusion transcripts from RNA-Seq data. Three novel (KIAA2026-NUDT11, CCBL1-ARL1, and AFF3-PHF1) and two previously known fusions (FUS-CREB3L2 and HAS2-PLAG1) were found and could be verified by other methods. These findings show that RNA-Seq is a powerful tool for detecting gene fusions in sarcomas but also suggest that it is advisable to use more than one algorithm to analyze the output data as only two of the confirmed fusions were reported by more than one of the gene fusion detection software programs. For all of the confirmed gene fusions, at least one of the genes mapped to a chromosome band implicated by the karyotype, suggesting that sarcomas with simple karyotypes constitute an excellent resource for identifying novel gene fusions.Laboratory Investigation advance online publication, 13 April 2015; doi:10.1038/labinvest.2015.50. (Less)
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type
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published
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in
Laboratory Investigation
volume
95
issue
6
pages
603 - 609
publisher
Nature Publishing Group
external identifiers
  • pmid:25867764
  • wos:000355145600003
  • scopus:84930017015
ISSN
1530-0307
DOI
10.1038/labinvest.2015.50
language
English
LU publication?
yes
id
b660495a-d411-4374-8b5f-b31df816e17b (old id 5342019)
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http://www.ncbi.nlm.nih.gov/pubmed/25867764?dopt=Abstract
date added to LUP
2015-05-05 20:42:28
date last changed
2017-07-09 03:14:33
@article{b660495a-d411-4374-8b5f-b31df816e17b,
  abstract     = {Gene fusions are neoplasia-associated mutations arising from structural chromosomal rearrangements. They have a strong impact on tumor development and constitute important diagnostic markers. Malignant soft tissue tumors (sarcomas) constitute a heterogeneous group of neoplasms with >50 distinct subtypes, each of which is rare. In addition, there is considerable morphologic overlap between sarcomas and benign lesions. Several subtypes display distinct gene fusions, serving as excellent biomarkers. The development of methods for deep sequencing of the complete transcriptome (RNA-Seq) has substantially improved the possibilities for detecting gene fusions. With the aim of identifying new gene fusions of biological and clinical relevance, eight sarcomas with simple karyotypes, ie, only one or a few structural rearrangements, were subjected to massively parallel paired-end sequencing of mRNA. Three different algorithms were used to identify fusion transcripts from RNA-Seq data. Three novel (KIAA2026-NUDT11, CCBL1-ARL1, and AFF3-PHF1) and two previously known fusions (FUS-CREB3L2 and HAS2-PLAG1) were found and could be verified by other methods. These findings show that RNA-Seq is a powerful tool for detecting gene fusions in sarcomas but also suggest that it is advisable to use more than one algorithm to analyze the output data as only two of the confirmed fusions were reported by more than one of the gene fusion detection software programs. For all of the confirmed gene fusions, at least one of the genes mapped to a chromosome band implicated by the karyotype, suggesting that sarcomas with simple karyotypes constitute an excellent resource for identifying novel gene fusions.Laboratory Investigation advance online publication, 13 April 2015; doi:10.1038/labinvest.2015.50.},
  author       = {Hofvander, Jakob and Tayebwa, Johnbosco and Nilsson, Jenny and Magnusson, Linda and Brosjö, Otte and Larsson, Olle and Vult von Steyern, Fredrik and Domanski, Henryk and Mandahl, Nils and Mertens, Fredrik},
  issn         = {1530-0307},
  language     = {eng},
  number       = {6},
  pages        = {603--609},
  publisher    = {Nature Publishing Group},
  series       = {Laboratory Investigation},
  title        = {RNA sequencing of sarcomas with simple karyotypes: identification and enrichment of fusion transcripts.},
  url          = {http://dx.doi.org/10.1038/labinvest.2015.50},
  volume       = {95},
  year         = {2015},
}