Interpreting pathways to discover cancer driver genes with Moonlight
Recommended Citation
Colaprico A, Olsen C, Bailey MH, Odom GJ, Terkelsen T, Silva TC, Olsen AV, Cantini L, Zinovyev A, Barillot E, Noushmehr H, Bertoli G, Castiglioni I, Cava C, Bontempi G, Chen XS, and Papaleo E. Interpreting pathways to discover cancer driver genes with Moonlight. Nat Commun 2020; 11(1):69.
Document Type
Article
Publication Date
1-3-2020
Publication Title
Nat Commun
Abstract
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.
PubMed ID
31900418
Volume
11
Issue
1
First Page
69
Last Page
69
