Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas.

Published

Journal Article

Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling; chromatin, translation, and DNA replication/repair were conserved pan-cancer. This analysis reveals insights into MYC biology and is a reference for biomarkers and therapeutics for cancers with alterations of MYC or the PMN.

Full Text

Duke Authors

Cited Authors

  • Schaub, FX; Dhankani, V; Berger, AC; Trivedi, M; Richardson, AB; Shaw, R; Zhao, W; Zhang, X; Ventura, A; Liu, Y; Ayer, DE; Hurlin, PJ; Cherniack, AD; Eisenman, RN; Bernard, B; Grandori, C; Cancer Genome Atlas Network,

Published Date

  • March 2018

Published In

Volume / Issue

  • 6 / 3

Start / End Page

  • 282 - 300.e2

PubMed ID

  • 29596783

Pubmed Central ID

  • 29596783

Electronic International Standard Serial Number (EISSN)

  • 2405-4720

International Standard Serial Number (ISSN)

  • 2405-4712

Digital Object Identifier (DOI)

  • 10.1016/j.cels.2018.03.003

Language

  • eng