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

F. X. Schaub, V. Dhankani, A. C. Berger, M. Trivedi, A. B. Richardson, R. Shaw, W. Zhao, X. Zhang, A. Ventura, Y. Liu, D. E. Ayer, P. J. Hurlin, A. D. Cherniack, R. N. Eisenman, B. Bernard, C. Grandori, Cancer Genome Atlas Network

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)282-300.e2
JournalCell Systems
Volume6
Issue number3
DOIs
Publication statusPublished - Mar 28 2018
Externally publishedYes

Fingerprint

Atlases
Oncogenes
Genome
Neoplasms
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

Cite this

Schaub, F. X., Dhankani, V., Berger, A. C., Trivedi, M., Richardson, A. B., Shaw, R., ... Network, C. G. A. (2018). Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas. Cell Systems, 6(3), 282-300.e2. https://doi.org/10.1016/j.cels.2018.03.003.

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

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

Research output: Contribution to journalArticle

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 & Network, CGA 2018, 'Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas', Cell Systems, vol. 6, no. 3, pp. 282-300.e2. https://doi.org/10.1016/j.cels.2018.03.003.
Schaub FX, Dhankani V, Berger AC, Trivedi M, Richardson AB, Shaw R et al. Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas. Cell Systems. 2018 Mar 28;6(3):282-300.e2. https://doi.org/10.1016/j.cels.2018.03.003.
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. ; Network, Cancer Genome Atlas. / 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.

AB - 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.

KW - MAX

KW - MNT

KW - MYC genomic alterations

KW - TCGA

KW - The Cancer Genome Atlas

U2 - 10.1016/j.cels.2018.03.003.

DO - 10.1016/j.cels.2018.03.003.

M3 - Article

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SP - 282-300.e2

JO - Cell Systems

JF - Cell Systems

SN - 2405-4712

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