Abstract 5196: Different miRNAs expression in leiomyosarcoma and undifferentiated pleomorphic sarcoma

2014 
Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Rare and highly aggressive adult soft tissue sarcomas, leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma (UPS), contain complex genomics characterized by a multitude of rearrangements, amplifications and deletions. Since differential diagnosis between the two sarcoma histotypes continues to remain a challenge, we attempted to identify a specific signature useful for improving the differential diagnosis, and we performed miRNA profiling on series of LMS and UPS samples stored at Rizzoli biobank. First, we investigated the different miRNA expression profile in 20 primary sarcoma samples, 10 high-grade LMS and 10 UPS, MFH-like, using miRNA array technique. The top 5 differentially expressed (p<0.01) miRNAs (miR-199b-5p, miR-320a, miR-199a-3p, miR-126, miR-22) were validated by RT-PCR on a series of further 27 UPS and 21 LMS. Confirming our microarray data, an higher expression of miR-199-5p and a lower expression of miR-320a was seen in UPS when compared to LMS. To evaluate the potential role of the above selected miRNAs, the gene targets recognized by three different target prediction databases (miRBase, TargetScan , miRanda) were combined with a list of LMS- and UPS-associated genes reported in literature. From an integrated analysis, IMP3, ROR2, MDM2, CDK4, and UPA genes were identified. By immunohistochemistry analysis, most of them showed strong protein expression in LMS group. Our data suggest a potential role of miR-320a and miR-199-5p in LMS and UPS development and expand our knowledge about these complex sarcoma histotypes. Association analysis between expression and chromosomal locations of miRNAs are ongoing to identify chromosomal regions involved in these tumors. Citation Format: Laura Pazzaglia, Mohamed Guled, Ioana Borze, Maria Serena Benassi, Piero Picci, Sakari Knuutila. Different miRNAs expression in leiomyosarcoma and undifferentiated pleomorphic sarcoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5196. doi:10.1158/1538-7445.AM2014-5196
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