Abstract 4818: Array-CGH and miRNA expression profiling of triple negative breast cancer in African-American women
Authors: Regis Kenny , Jaldin Michelle , Mahajan Akanksha , Duttargi Anju , Sheahan Laura , Gusev Yuriy , Madhavan Subha , Cavalli Luciane R. 
Published: August 2015

In the African-American (AA) population, an increased incidence and shorter survival rate of triple negative breast cancer (TNBC) has been reported when compared to White women, with their cancer usually diagnosed in more advanced stages and with non-localized disease. The main objective of our study is to identify molecular markers in TNBC in AA patients that may be associated with their observed disparity in incidence and mortality rates. Formalin-fixed paraffin-embedded tumor sections were obtained from 26 and 28 cases of TNBC from AA and Caucasian breast cancer patients, respectively, and analyzed for DNA copy number (Agilent-SurePrint G3 Human CGH Microarray 8×60K) and miRNA expression (Nanostring System) alterations. The cases were obtained with clinically annotated data from the Histopathology Shared Resources at the Lombardi Comprehensive Cancer Center. The miRNA data was directly integrated with the array-CGH data from the same cases. Combinatorial target predicted algorithms in conjunction with functional and pathway annotation enrichment systems were performed to identify predicted target functions. A distinct DNA copy number profile was observed between TNBC of AA and Caucasian cases: the cytobands differentially involved in the AA-TNBC cases were 7p22.3-22.1, 12p13.33-p11.1, 17q25.3 and 17p13.3-p11.2. Common cytobands in both groups were 1q21.1-q44, 8q22.1-q24.3, 16p13.33-p11.1 and 20q11.2-q13.12. An average of 30.5 and 16.8 DNA copy alterations were observed between the AA and Caucasian cases respectively and the miRNA profiling revealed 209 miRNAs differentially expressed between the groups. Unsupervised hierarchical clustering analysis separated the cases by ethnicity (with the exception of 6 cases). Among the miRNAs observed with higher and lower expression levels in the AA cases were miR150-5p, miR4286, miR29b3p and miR1283, miR1253, miR378e, respectively. Ingenuity pathway analysis identified molecular and cellular functions mostly related to cellular development, growth, proliferation and movement, and cell death and survival. Clinical pathological data analysis revealed higher tumor grades and stages in the TNBC of AA women when compared to Caucasians; association of these parameters with the genomic and expression miRNA data is being performed. In conclusion, a distinct DNA copy number and miRNA profile was observed in the AA-TNBC cases when compared to the Caucasians cases of our study. These initial findings will provide the basis for the functional analysis of the identified molecular markers and their potential prognostic and therapeutic impact for this group. In addition to providing a better understanding of the biology of their tumors, these analyses can reveal molecular targets for tailored and ethnic-based clinical trials, which can ultimately lead to the reduction of the observed cancer disparity.

Support: FDA U01 FD004319, NIH-NIGMS GM101997 and Susan Komen Foundation.

Citation Format: Kenny Regis, Michelle Jaldin, Akanksha Mahajan, Anju Duttargi, Laura Sheahan, Yuriy Gusev, Subha Madhavan, Luciane R. Cavalli. Array-CGH and miRNA expression profiling of triple negative breast cancer in African-American women. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4818. doi:10.1158/1538-7445.AM2015-4818