Diagenode

Predicting interactome networks perturbations in human cancer: application to gene fusions in acute lymphoblastic leukemia.


Juvenal Hajingabo L, Daakour S, Martin M, Grausenburger R, Panzer-Grümayer R, Dequiedt F, Simonis N, Twizere JC

Genomic variations such as point mutations and gene fusions are directly or indirectly associated with human diseases. They are recognized as diagnostic, prognostic markers and therapeutic targets. However, predicting the functional impact of these genetic alterations beyond affected genes and their products is challenging because diseased phenotypes are likely dependent of complex molecular interaction networks. Using as models three different chromosomal translocations ETV6-RUNX1 (TEL-AML1), BCR-ABL1, and TCF3-PBX1 (E2A-PBX1), frequently found in precursor-B cell acute lymphoblastic leukemia (preB-ALL), we develop an approach to extract perturbed molecular interactions from gene expression changes. We show that the MYC and JunD transcriptional circuits are specifically deregulated following ETV6-RUNX1 and TCF3-PBX1 gene fusions, respectively. We also identified the bulk mRNA NXF1-dependent machinery as a direct target for the TCF3-PBX1 fusion protein. Through a novel approach combining gene expression and interactome data analysis, we provide new insight into TCF3-PBX1 and ETV6-RUNX1 acute lymphoblastic leukemia.

Tags
Bioruptor
Chromatin Shearing
ChIP-seq

Share this article

Published
October, 2014

Source

Events

 See all events

Twitter feed

News

 See all news