ArticleThe Journal of clinical investigation2014
MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 284 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
284 citing papers in PubMed, 2 syntheses or guidelines pooled it, 465 citations in OpenAlex.
- A multimodal atlas of tumour metabolism reveals the architecture of gene-metabolite covariation.Nature metabolism · 2023Pooled it
- The Significance of SIX1 as a Prognostic Biomarker for Survival Outcome in Various Cancer Patients: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2021Pooled it
- Trial
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- Circulating Dipeptides in Cancer: Degradation Fragments or Functional Metabolites?International journal of molecular sciences · 2026Review
- CSIE: cancer subtyping via inference and ensemble.Briefings in bioinformatics · 2026Article
- Constitutive AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity.Science advances · 2026Article
- Mitochondrial uncoupling inhibits serine catabolismCancer biology & medicine · 2026Article
- Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer.Current oncology (Toronto, Ont.) · 2026Review
- Multi-Modal Metabolomics Deciphers Pan-Cancer Metabolic Landscapes and Spatial-Niche-Specific Alternations.Metabolites · 2026Article
- 2-Hydroxyglutarate in onco-pathway: a metabolic driver of proto-oncogene activation.Frontiers in oncology · 2026Review
- Fast multimodal imaging combined with machine learning identifying taurine as a potential marker for breast cancer margin assessment.NPJ digital medicine · 2025Article
- Feature learning augmented with sampling and heuristics (FLASH) improves model performance and biomarker identification.NPJ systems biology and applications · 2025Article
- Comparative metabolomics reveals specific metabolic signatures in colorectal cancer cell line models.Discover oncology · 2025Article
- In Silico Analysis of the Role of Estrogen Signaling in the Expression of Metabolic Genes in Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- SMART 2.0 Statistical Metabolomics Analysis: An R Tool 2.0.Analytical chemistry · 2025Article
- DSCC: disease subtyping using spectral clustering and community detection from consensus networks.Briefings in bioinformatics · 2025Article
224 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
34 authors at 8 institutions in 1 country.
Funding
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 frequency in African-American patients. Tumors of this subtype had a stem cell-like transcriptional signature and tended to overexpress glutaminase, suggestive of a functional relationship between glutamine and 2HG metabolism in breast cancer. Accordingly, 13C-labeled glutamine was incorporated into 2HG in cells with aberrant 2HG accumulation, whereas pharmacologic and siRNA-mediated glutaminase inhibition reduced 2HG levels. Our findings implicate 2HG as a candidate breast cancer oncometabolite associated with MYC activation and poor prognosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.