W. Rathmell
Last active: 11/27/2019

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

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
Cell Syst. 2018 6 (3): 282-300.e2

PMID: 29596783 · PMCID: PMC5892207 · DOI:10.1016/j.cels.2018.03.003

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.

Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

MeSH Terms (17)

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Basic Helix-Loop-Helix Transcription Factors Biomarkers, Tumor Carcinogenesis Chromatin Computational Biology Genes, myc Genomics Genomics Humans Neoplasms Oncogenes Proteomics Proto-Oncogene Proteins c-myc Repressor Proteins Signal Transduction Transcription Factors

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