Systematic Analysis Reveals that Cancer Mutations Converge on Deregulated Metabolism of Arachidonate and Xenobiotics
Artikel i vetenskaplig tidskrift, 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

Författare

Francesco Gatto

Chalmers, Biologi och bioteknik, Systembiologi

A. Schulze

Comprehensive Cancer Center Mainfranken

Julius-Maximilians Universität Würzburg

Jens B Nielsen

Chalmers, Biologi och bioteknik, Systembiologi

Cell Reports

22111247 (eISSN)

Vol. 16 3 878-895

Ämneskategorier

Cellbiologi

Styrkeområden

Livsvetenskaper och teknik (2010-2018)

DOI

10.1016/j.celrep.2016.06.038

PubMed

27396332

Mer information

Senast uppdaterat

2021-01-21