Recurrent PRDM10 Gene Fusions in Undifferentiated Pleomorphic Sarcoma.
(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:
https://lup.lub.lu.se/record/4908102
- author
- 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
- organization
- publishing date
- 2015
- 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
- pmid:25516889
- 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
- 2016-04-01 10:15:35
- date last changed
- 2022-03-19 19:02:47
@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}}, doi = {{10.1158/1078-0432.CCR-14-2399}}, volume = {{21}}, year = {{2015}}, }