Recurrent PRDM10 Gene Fusions in Undifferentiated Pleomorphic Sarcoma.
Author
Summary, in English
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.
Department/s
- The genetics of soft tissue tumors
- Division of Clinical Genetics
- Orthopaedics (Lund)
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2015
Language
English
Pages
864-869
Publication/Series
Clinical Cancer Research
Volume
21
Issue
4
Links
Document type
Journal article
Publisher
American Association for Cancer Research
Topic
- Cancer and Oncology
Status
Published
Research group
- The genetics of soft tissue tumors
ISBN/ISSN/Other
- ISSN: 1078-0432