Abstract 3004: Specific microRNAs associate with aggressive breast tumor phenotypes in an ethnically diverse patient cohort
Authors: Nwachukwu Chika , Zhang Chunling , Duan Shiwei , Huo Dezheng , Minn Andy , Perou Charles , Olopade Olufunmilayo 
Published: February 2011

Background: Sporadic basal like breast cancer (BLC), a subset of triple negative tumors with bad prognosis appears to be overrepresented in young women and women of African Ancestry. The molecular drivers of basal like and triple negative tumors have not been identified and there is a lack of targeted therapies for women with these tumor phenotypes. MicroRNAs (miRNAs), a new class of small non-coding RNAs, are known to regulate expression of genes important for several biological processes including stem cell division, apoptosis and cell proliferation. Thus, miRNAs have been linked to several diseases including cancer. To examine whether miRNAs play a role in the development and progression of breast cancer, we analyzed 47 primary breast tumors. We hypothesize that specific miRNAs will be associated with particular subtypes of breast cancer especially the biologically aggressive basal like subtype.

Materials and Methods: To test our hypothesis, we used a number of complementary approaches 1.) Using exiqon's miRNA microarray, we profiled 47 breast tumors enriched for African Americans and 4 adjacent normal samples for expression of all known miRNAs. Real time RT-PCR was used to validate the expression data 2.) All tumor samples were classified into the known molecular subtypes using DNA microarray and surrogate immunohistochemistry markers 3.) A subset of the patients with paired normal and tumor samples were analyzed for genomic alterations including deletions and amplifications using 100k Illumina SNP array to corroborate the expression data.

Results: The diverse patient cohort included 36 African Americans, 10 Whites, 1 Hispanic; median age was 51 years. The tumor subtypes included 13 basal like, 11 HER2, 9 Luminal A, 7 Luminal B and 5 normal like. We found 151 miRNA were differentially expressed between primary triple negative and non triple negative tumors. We also found 17 miRNAs that were down regulated in basal tumors. More importantly, some of the 17 microRNAs downregulated in primary BLCs were miRNAs already identified to play a role in de-differentiation or epithelial to mesenchymal transition, all characteristics of BLC. Lastly, some of the miRNAs downregulated in primary BLCs were located at chromosomal regions that are frequently deleted in basal like tumors.

Conclusion: Our data suggests that miRNAs downregulated in BLCs can be lost by several genomic mechanisms and more importantly loss of expression of specific miRNAs may play important roles in development of tumors with this phenotype. Ongoing work is aimed at examining the molecular mechanisms whereby specific miRNAs contribute to the development of basal like tumors.and in understanding the clinical implications of differentially expressed miRNAs in breast tumor progression. These studies underscore the need for an integrated genomic approach to understand breast cancer pathogenesis in diverse populations.

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 3004.