Recurrent PRDM10 gene fusions in undifferentiated pleomorphic sarcoma

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Undifferentiated pleomorphic sarcoma (UPS) is a high-grade sarcoma lacking identifiable differentiation.
• Current diagnostic and therapeutic strategies for UPS are limited by the absence of specific genetic markers.
• The metastatic rate for UPS is approximately one-third, highlighting the need for better prognostic indicators.

Purpose of the Study:

• To identify novel gene fusions in undifferentiated pleomorphic sarcoma (UPS) using transcriptome sequencing (RNA-Seq).
• To investigate potential genetic alterations that could aid in the stratification and treatment of UPS.

Main Methods:

• Transcriptome sequencing (RNA-Seq) was performed on soft tissue sarcomas.
• Fluorescence in situ hybridization (FISH) and various PCR methodologies were employed to detect gene fusions and rearrangements.
• The study analyzed a cohort of 84 soft tissue sarcomas, focusing on the PRDM10 gene.

Main Results:

• Two novel gene fusions involving PRDM10 were identified in UPS cases using RNA-Seq.
• These fusions involved PRDM10 as the 3' partner and either MED12 or CITED2 as the 5' partner.
• An additional case of MED12/PRDM10 fusion was found in a larger cohort, suggesting PRDM10 fusions occur in approximately 5% of UPS.

Conclusions:

• PRDM10 fusions represent a newly identified genetic alteration in a subset of UPS.
• While morphologically similar to other UPS, the PRDM10 fusion-positive cases were low-grade and did not metastasize.
• PRDM10 fusion-positive sarcomas may represent a clinically significant subgroup of UPS with a favorable prognosis.