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

The Cancer Genome Atlas Network

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)282-300.e2
JournalCell Systems
Volume6
Issue number3
DOIs
StatePublished - Mar 28 2018

Fingerprint

Atlases
Oncogenes
Genome
Neoplasms
Neoplasm Genes
Immunologic Factors
Tumor Biomarkers
DNA Replication
DNA Repair
Proteomics
Chromatin
Intercellular Signaling Peptides and Proteins
Transcription Factors

Keywords

  • MAX
  • MNT
  • MYC genomic alterations
  • TCGA
  • The Cancer Genome Atlas

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Cite this

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

In: Cell Systems, Vol. 6, No. 3, 28.03.2018, p. 282-300.e2.

Research output: Contribution to journalArticle

The Cancer Genome Atlas Network. / Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas. In: Cell Systems. 2018 ; Vol. 6, No. 3. pp. 282-300.e2.
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N2 - 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.

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