Abstract IA30: Insights into metabolome of breast cancer

Abstract

Abstract Metabolomics describes the science of quantifying the levels of metabolites (e.g., small molecules <1kDa) that are the byproducts of cellular metabolism. Unlike genomics, transcriptomics and proteomics, metabolomic analysis involves reduced complexity because of fewer endpoints and allows the assay of composite downstream outputs from complex interconnected cellular processes. These aspects both facilitate bioinformatic analysis and may accentuate subtle upstream gene/protein level alterations. Comparisons of metabolomic profiles from tissues or bodily fluids from one diseased state to another permits the identification of pathways and processes that may drive the phenotype in question. Our recent profiling of 200 metabolites using mass spectrometry in benign and malignant breast tissues from ancestry-verified AA and EA women, revealed altered levels of specific metabolites (or associated pathways) in AA TN BCa compared to EA TN tumors. Key among them was elevated levels of 2- hydroxyglutaric acid (2-HG), a mitochondrial onco-metabolite that was elevated in a subset of predominantly AA TN BCa with poor clinical outcome. Tumors with high 2-HG had a distinct methylation signature exhibiting activation of the MYC oncogene and were associated with elevated levels of fatty acids and lipids. Taken together, we expect these studies help understand the disparity in the clinical behavior of TN BCa. Further, we expect biochemical profiles to be useful in stratifying tumors for various pathway-based treatment regimens. Citation Format: Arun Sreekumar. Insights into metabolome of breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr IA30.