Systematic Analysis Reveals that Cancer Mutations Converge on Deregulated Metabolism of Arachidonate and Xenobiotics
Journal article, 2016

Mutations are the basis of the clonal evolution of most cancers. Nevertheless, a systematic analysis of whether mutations are selected in cancer because they lead to the deregulation of specific biological processes independent of the type of cancer is still lacking. In this study, we correlated the genome and transcriptome of 1,082 tumors. We found that nine commonly mutated genes correlated with substantial changes in gene expression, which primarily converged on metabolism. Further network analyses circumscribed the convergence to a network of reactions, termed AraX, that involves the glutathione- and oxygen-mediated metabolism of arachidonic acid and xenobiotics. In an independent cohort of 4,462 samples, all nine mutated genes were consistently correlated with the deregulation of AraX. Among all of the metabolic pathways, AraX deregulation represented the strongest predictor of patient survival. These findings suggest that oncogenic mutations drive a selection process that converges on the deregulation of the AraX network.

reductases

genome

fatty-acids

landscape

gene-expression

cytochrome-p450 4x1

network

set

discovery

carcinoma

Author

Francesco Gatto

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

A. Schulze

Comprehensive Cancer Center Mainfranken

University of Würzburg

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Cell Reports

22111247 (eISSN)

Vol. 16 3 878-895

Subject Categories

Cell Biology

Areas of Advance

Life Science Engineering (2010-2018)

DOI

10.1016/j.celrep.2016.06.038

PubMed

27396332

More information

Latest update

1/21/2021