Determination Of Microrna Expression Profile In Tumors From Young Women With Breast Cancer

Background: MicroRNAs (miRNA) are endogenous small non-coding RNAs which regulate the expression of many important protein-coding genes in a sequence-specific approach. MicroRNAs generally play a role as negative regulators of mRNA translation and stability. Each of miRNA binds to many critical targets related to cell proliferation, cell differentiation and cell death. MicroRNAs have been shown to be strongly related to human cancer and could suggest new disease conduction. However the miRNA signature profile has not been explored in tumors from young women with Breast Cancer which have been correlated with poor survival and aggressive features. Methods/Results: Fifty tumor tissues from brazilian patients diagnosed with ductal infiltrative breast carcinoma before the age of 35, were obtained from AC. Camargo Hospital and Hospital de Cancer de Barretos, SP, Brazil. BRCA1/2 status was analyzed. For an initial study, twenty patients were selected: 10 with familial history of breast and ovarian suggestive of hereditary condition according to NCCN criteria and 10 without familial history. Patients of both groups were of non carriers of BRCA1/2 mutations. Total RNA isolation from each tumor was successfully done with RNeasy Mini Kit (Qiagen). The determination of microRNA expression profile between those 2 groups was performed by TaqMan microRNA Assay (Applied Biosystem), composed by 384 miRNAs assays. All real time PCR reactions were performed using a 7900 System Real Time PCR cycler (Applied Biosystem) according to manufacturer instructions. Relative quantification of miRNA expression was calculated with the delta Ct method based on average threshold 0.2 (SDS Applied Biosystem software). Data were normalized using endogenous miRNA presented in each array. Statistical comparisons were performed using Student T test with adjusted Bonferroni correction. 81 miRNAs were differentially expressed between the two groups of patients. Among these miRNAs some which were upregulated in tumors of patients with a familial history and downregulated in the other group have been previously described in breast cancer such as: miR-202, miR-221, miR-371-3p, miR-384, miR-561 and miR-660. It was found that miR-129-5p, miR-219-5p, miR-487a and miR-510 were superexpressed in the sporadic cases. MicroRNA predicted targets were downloaded from three websites: PicTar, TargetScanHuman and miRanda. A number of predicted targets included the estrogen receptor (ESR1), p53, BRCA2, PTEN, ERCC6 among others. Conclusion: Our data suggested that tumors from familial or sporadic cases presented particular miRNA expression patterns suggestive of alternative molecular pathways of the disease. This is the first evidence of miRNA expression in tumors of early onset breast cancer tumors patients, suggesting the possibility that miRNA genes may lead to the new biomarkers detection for tumors of BRCA1/2 non carrier9s patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3038.