Pan-cancer alterations of the MYC oncogene and Its proximal network across the Cancer Genome Atlas Journal Article

Authors: Schaub, F. X.; Dhankani, V.; Berger, A. C.; Trivedi, M.; Richardson, A. B.; Shaw, R.; Zhao, W.; Zhang, X.; Ventura, A.; Liu, Y.; Ayer, D. E.; Hurlin, P. J.; Cherniack, A. D.; Eisenman, R. N.; Bernard, B.; Grandori, C.; Cancer Genome Atlas Network
Article Title: Pan-cancer alterations of the MYC oncogene and Its proximal network across the Cancer Genome Atlas
Abstract: 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. We present a computational study determining the frequency and extent of alterations of the MYC network across the 33 human cancers of TCGA. These data, together with MYC, positively correlated pathways as well as mutually exclusive cancer genes, will be a resource for understanding MYC-driven cancers and designing of therapeutics. © 2018 The Authors
Keywords: signal transduction; controlled study; unclassified drug; gene deletion; dna replication; dna repair; microrna; protein; cancer genetics; tumor suppressor gene; immune response; human genome; myc protein; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; b raf kinase; genetic conservation; apc protein; oncogene myc; functional proteomics; tcga; the cancer genome atlas; human; priority journal; article; max; malignant neoplasm; pik3ca protein; mnt; myc genomic alterations
Journal Title: Cell Systems
Volume: 6
Issue: 3
ISSN: 2405-4712
Publisher: Elsevier Inc.  
Date Published: 2018-03-28
Start Page: 282
End Page: 300.e2
Language: English
DOI: 10.1016/j.cels.2018.03.003
PROVIDER: scopus
PMCID: PMC5892207
PUBMED: 29596783
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
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MSK Authors
  1. Andrea Ventura
    39 Ventura