MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis.

MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis. J Clin Invest. 2013 Dec 9; Authors: Terunuma A, Putluri N, Mishra P, Mathé EA, Dorsey TH, Yi M, Wallace TA, Issaq HJ, Zhou M, Killian JK, Stevenson HS, Karoly ED, Chan K, Samanta S, Prieto D, Hsu TY, Kurley SJ, Putluri V, Sonavane R, Edelman DC, Wulff J, Starks AM, Yang Y, Kittles RA, Yfantis HG, Lee DH, Ioffe OB, Schiff R, Stephens RM, Meltzer PS, Veenstra TD, Westbrook TF, Sreekumar A, Ambs S Abstract Metabolic profiling of cancer cells has recently been established as a promising tool for the development of therapies and identification of cancer biomarkers. Here we characterized the metabolomic profile of human breast tumors and uncovered intrinsic metabolite signatures in these tumors using an untargeted discovery approach and validation of key metabolites. The oncometabolite 2-hydroxyglutarate (2HG) accumulated at high levels in a subset of tumors and human breast cancer cell lines. We discovered an association between increased 2HG levels and MYC pathway activation in breast cancer, and further corroborated this relationship using MYC overexpression and knockdown in human mammary epithelial and breast cancer cells. Further analyses revealed globally increased DNA methylation in 2HG-high tumors and identified a tumor subtype with high tissue 2HG and a distinct DNA methylation pattern that was associated with poor prognosis and occurred with higher f...
Source: Clinical Breast Cancer - Category: Cancer & Oncology Authors: Tags: J Clin Invest Source Type: research