Recurrent PRDM10 Gene Fusions in Undifferentiated Pleomorphic Sarcoma
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Date
2015
Journal Title
Journal ISSN
Volume Title
Publisher
Clinical Cancer Research
Abstract
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 one third. 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, FISH, 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 30 partner and either MED12 or CITED2 as the 50
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.
Description
Keywords
PRDM10 Gene Fusions, Pleomorphic Sarcoma
Citation
Hofvander, J., Tayebwa, J., Nilsson, J., Magnusson, L., Brosjö, O., Larsson, O., ... & Mertens, F. (2015). Recurrent PRDM10 Gene Fusions in Undifferentiated Pleomorphic SarcomaPRDM10 Fusions in UPS. Clinical Cancer Research, 21(4), 864-869. doi: 10.1158/1078-0432.CCR-14-2399