Amplification Of Mir-26a-2 In Human Liposarcoma Is Correlated With Poor Patient Survival

Human liposarcoma (LPS) is one of the most common soft tissue sarcomas in adults. However, its molecular mechanism is poorly understood. For better understanding of the disease, we examined 54 human liposarcoma samples including 51 primary tumors and 3 cell lines (SW872, LP6, LP141) using Affymetrix 250K single nucleotide polymorphism (SNP) array. Allele-specific copy number (CN) analysis using anonymous references revealed that CN gain was dominant event over CN loss and loss of heterozygosity (LOH) in human LPS. Recurrent CN gain at 1q21–24 (43% of the samples), 5p13-p15 (46%), and 8q24 (41%) were identified. The most prominent CN gain was found in the 12q13-q15 region. 88% of the samples, mostly well-differentiated / de-differentiated subtype (WDLPS / DDLPS), showed various levels of CN gains centered at MDM2 gene. In addition to MDM2 amplicon, we also identified an MDM2-independent amplicon in the 12q13-q15 region centered at miR-26a-2 gene at the same frequency (88%). MDM2 amplicon almost always accompanied miR-26a-2 amplicon. Likewise, samples without MDM2 amplicon did not have a miR-26a-2 amplicon. Quantitative reverse transcription real-time PCR (qRT-PCR) analysis showed that this CN gain of miR-26a-2 was strongly correlated with high mRNA expression of the gene in the WDLPS / DDLPS subtype. Furthermore, high mRNA expression of miR-26a-2 significantly correlated with a worse patient survival (p=0.05). Interestingly, some samples in myxoid / round-cell subtype (MRC) also showed high expression of miR-26a-2 without any prominent CN changes. High expression in the MRC subtype was also correlated with poor patient survival (p=0.0029). Western blot analysis using LPS cell lines revealed that cells with high miR-26a-2 expression showed decreased levels of RB1 and PTEN, which are two verified targets of miR-26a-2. In conclusion, our analysis demonstrated the clinical importance of miR-26a-2 gene in human LPS. This finding may contribute to the discovery of prognostic markers as well as novel therapeutic targets for human LPS. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-345. doi:10.1158/1538-7445.AM2011-LB-345