Abstract 4936: MicroRNAs located on 13q and 20q are differentially expressed between normal mucosa, adenomas and carcinomas of the large intestine

Abstract

Background: In colorectal cancer (CRC) miRNA expression profiling studies have reported differences in expression between colorectal carcinomas and controls, microsatellite stable, microsatellite instable and chromosomal instable tumors, and demonstrated prognostic value for some miRNAs. However, the role of miRNAs in CRC pathogenesis has been only partially investigated. CRC results from the gradual accumulation of multiple genetic and epigenetic changes in the colorectal epithelial cells. The majority of CRCs (85%) shows an accumulation of chromosomal abnormalities. In CRC, up to 15% of the annotated miRNAs are located at regions of chromosomal instability implicated in colorectal adenoma to carcinoma progression. Two of the most frequent chromosomal aberrations in CRC are gain of 13q (>50%) and gain of 20q (>65%). A total of 36 miRNAs are located on these chromosomal arms. However, the leading cause of the miRNA's aberrant expression and the pathways through which they contribute to CRC have not been elucidated. Aim: To investigate the expression of miRNAs located on 13q and 20q in normal colon mucosa, adenomas and CRC. Materials & Methods: DNA and total RNA was isolated from 48 colorectal adenomas, 51 CRCs and 10 normal mucosa samples. Multiplex Ligation-dependent Probe Amplification (MLPA) was used to determine DNA copy number gain of 13q and/or 20q. Expression levels of 17 miRNAs located on 13q and 19 miRNAs on 20q (miRBase release 15) were measured by TaqMan miRNA assays. Results: 11 Of the miRNAs located on 13q and 8 of the miRNAs located on 20q were detected in colon tissue. 15 Of these miRNAs were significantly differentially expressed between colorectal tumors compared to controls and 13 were differentially expressed between carcinomas and adenomas (p<0.05). In addition, 11 miRNAs were significantly differentially expressed between tumors with or without a 13q and/or 20q gain (p<0.05). Conclusion: Gene dosage effects of miRNAs located on chromosomes 13q and 20q play an important role in CRC progression, and taking this into account is essential to achieve a comprehensive understanding of the pathogenesis of this malignancy. 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 4936. doi:10.1158/1538-7445.AM2011-4936