Patient-matched analysis identifies deregulated networks in prostate cancer to guide personalized therapeutic intervention.

Fiche publication

Date publication

janvier 2021

Journal

American journal of cancer research

Auteurs

Membres identifiés du Cancéropôle Est :
Dr GRONEMEYER Hinrich , Dr MENDOZA Manuel

Tous les auteurs :
Kumar A, Kasikci Y, Badredine A, Azzag K, Quintyn Ranty ML, Zaidi F, Aragou N, Mazerolles C, Malavaud B, Mendoza-Parra MA, Vandel L, Gronemeyer H

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/34873462

Résumé

Prostate cancer (PrCa) is the second most common malignancy in men. More than 50% of advanced prostate cancers display the TMPRSS2-ERG fusion. Despite extensive cancer genome/transcriptome data, little is known about the impact of mutations and altered transcription on regulatory networks in the PrCa of individual patients. Using patient-matched normal and tumor samples, we established somatic variations and differential transcriptome profiles of primary ERG-positive prostate cancers. Integration of protein-protein interaction and gene-regulatory network databases defined highly diverse patient-specific network alterations. Different components of a given regulatory pathway were altered by novel and known mutations and/or aberrant gene expression, including deregulated ERG targets, and were validated by using a novel methodology. Consequently, different sets of pathways were altered in each individual PrCa. In a given PrCa, several deregulated pathways share common factors, predicting synergistic effects on cancer progression. Our integrated analysis provides a paradigm to identify druggable key deregulated factors within regulatory networks to guide personalized therapies.