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Recurrent PRDM10 Gene Fusions in Undifferentiated Pleomorphic Sarcoma.

Hofvander, Jakob LU ; Tayebwa, Johnbosco LU ; Nilsson, Jenny LU ; Magnusson, Linda LU ; Brosjö, Otte; Larsson, Olle L; Vult von Steyern, Fredrik LU ; Mandahl, Nils; Fletcher, Christopher and Mertens, Fredrik LU (2015) In Clinical Cancer Research 21(4). p.864-869
Abstract
Purpose: Undifferentiated pleomorphic sarcoma (UPS) is defined as a sarcoma with cellular pleomorphism and no identifiable line of differentiation. It is typically a high-grade lesion with a metastatic rate of about 1/3. No tumor-specific rearrangement has been identified and genetic markers that could be used for treatment stratification are lacking. We performed transcriptome sequencing (RNA-Seq) to search for novel gene fusions. Experimental design: RNA-Seq, fluorescence in situ hybridization, and/or various PCR methodologies were used to search for gene fusions and rearrangements of the PRDM10 gene in 84 soft tissue sarcomas. Results: Using RNA-Seq, two cases of UPS were found to display novel gene fusions, both involving the... (More)
Purpose: Undifferentiated pleomorphic sarcoma (UPS) is defined as a sarcoma with cellular pleomorphism and no identifiable line of differentiation. It is typically a high-grade lesion with a metastatic rate of about 1/3. No tumor-specific rearrangement has been identified and genetic markers that could be used for treatment stratification are lacking. We performed transcriptome sequencing (RNA-Seq) to search for novel gene fusions. Experimental design: RNA-Seq, fluorescence in situ hybridization, and/or various PCR methodologies were used to search for gene fusions and rearrangements of the PRDM10 gene in 84 soft tissue sarcomas. Results: Using RNA-Seq, two cases of UPS were found to display novel gene fusions, both involving the transcription factor PRDM10 as the 3'-partner and either MED12 or CITED2 as the 5'-partner gene. Further screening of 82 soft tissue sarcomas for rearrangements of the PRDM10 locus, revealed one more UPS with a MED12/PRDM10 fusion. None of these genes has been implicated in neoplasia-associated gene fusions before. Conclusions: Our results suggest that PRDM10-fusions are present in around 5% of UPS. Although the fusion-positive cases in our series showed the same nuclear pleomorphism and lack of differentiation as other UPS, it is noteworthy that all three were morphologically low-grade and that none of the patients developed metastases. Thus, PRDM10 fusion-positive sarcomas may constitute a clinically important subset of UPS. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Cancer Research
volume
21
issue
4
pages
864 - 869
publisher
American Association for Cancer Research
external identifiers
  • pmid:25516889
  • wos:000349851200024
  • scopus:84923197172
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-14-2399
language
English
LU publication?
yes
id
0803da94-b7d5-44ff-b689-9a4edf02bac4 (old id 4908102)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25516889?dopt=Abstract
date added to LUP
2015-01-07 15:56:02
date last changed
2017-04-02 03:07:10
@article{0803da94-b7d5-44ff-b689-9a4edf02bac4,
  abstract     = {Purpose: Undifferentiated pleomorphic sarcoma (UPS) is defined as a sarcoma with cellular pleomorphism and no identifiable line of differentiation. It is typically a high-grade lesion with a metastatic rate of about 1/3. No tumor-specific rearrangement has been identified and genetic markers that could be used for treatment stratification are lacking. We performed transcriptome sequencing (RNA-Seq) to search for novel gene fusions. Experimental design: RNA-Seq, fluorescence in situ hybridization, and/or various PCR methodologies were used to search for gene fusions and rearrangements of the PRDM10 gene in 84 soft tissue sarcomas. Results: Using RNA-Seq, two cases of UPS were found to display novel gene fusions, both involving the transcription factor PRDM10 as the 3'-partner and either MED12 or CITED2 as the 5'-partner gene. Further screening of 82 soft tissue sarcomas for rearrangements of the PRDM10 locus, revealed one more UPS with a MED12/PRDM10 fusion. None of these genes has been implicated in neoplasia-associated gene fusions before. Conclusions: Our results suggest that PRDM10-fusions are present in around 5% of UPS. Although the fusion-positive cases in our series showed the same nuclear pleomorphism and lack of differentiation as other UPS, it is noteworthy that all three were morphologically low-grade and that none of the patients developed metastases. Thus, PRDM10 fusion-positive sarcomas may constitute a clinically important subset of UPS.},
  author       = {Hofvander, Jakob and Tayebwa, Johnbosco and Nilsson, Jenny and Magnusson, Linda and Brosjö, Otte and Larsson, Olle L and Vult von Steyern, Fredrik and Mandahl, Nils and Fletcher, Christopher and Mertens, Fredrik},
  issn         = {1078-0432},
  language     = {eng},
  number       = {4},
  pages        = {864--869},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {Recurrent PRDM10 Gene Fusions in Undifferentiated Pleomorphic Sarcoma.},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-14-2399},
  volume       = {21},
  year         = {2015},
}