Interpreting pathways to discover cancer driver genes with Moonlight

Research output: Contribution to journalJournal article

Documents

  • Antonio Colaprico
  • Catharina Olsen
  • Matthew H. Bailey
  • Gabriel J. Odom
  • Thilde Terkelsen
  • Tiago C. Silva
  • André V. Olsen
  • Laura Cantini
  • Andrei Zinovyev
  • Emmanuel Barillot
  • Houtan Noushmehr
  • Gloria Bertoli
  • Isabella Castiglioni
  • Claudia Cava
  • Gianluca Bontempi
  • Xi Steven Chen
  • Papaleo, Elena

Cancer driver gene alterations influence cancer development, occurring in oncogenes, tumor suppressors, and dual role genes. Discovering dual role cancer genes is difficult because of their elusive context-dependent behavior. We define oncogenic mediators as genes controlling biological processes. With them, we classify cancer driver genes, unveiling their roles in cancer mechanisms. To this end, we present Moonlight, a tool that incorporates multiple -omics data to identify critical cancer driver genes. With Moonlight, we analyze 8000+ tumor samples from 18 cancer types, discovering 3310 oncogenic mediators, 151 having dual roles. By incorporating additional data (amplification, mutation, DNA methylation, chromatin accessibility), we reveal 1000+ cancer driver genes, corroborating known molecular mechanisms. Additionally, we confirm critical cancer driver genes by analysing cell-line datasets. We discover inactivation of tumor suppressors in intron regions and that tissue type and subtype indicate dual role status. These findings help explain tumor heterogeneity and could guide therapeutic decisions.

Original languageEnglish
Article number69
JournalNature Communications
Volume11
Number of pages17
ISSN2041-1723
DOIs
Publication statusPublished - 2020

ID: 235774080