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

Schaub, Franz X; Dhankani, Varsha; Berger, Ashton C; Trivedi, Mihir; Richardson, Anne B; Shaw, Reid; Zhao, Wei; Zhang, Xiaoyang; Ventura, Andrea; Liu, Yuexin; Ayer, Donald E; Hurlin, Peter J; Cherniack, Andrew D; Eisenman, Robert N; Bernard, Brady; Grandori, Carla (2018). Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas. Cell systems, 6(3), 282-300.e2. Elsevier 10.1016/j.cels.2018.03.003

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2405-4712

Publisher:

Elsevier

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

01 Oct 2019 13:33

Last Modified:

22 Oct 2019 20:24

Publisher DOI:

10.1016/j.cels.2018.03.003

PubMed ID:

29596783

Additional Information:

Mark Rubin (Direktor DBMR) ist Collaborator in dieser Publikation.

Uncontrolled Keywords:

MAX MNT MYC genomic alterations TCGA The Cancer Genome Atlas

BORIS DOI:

10.7892/boris.126390

URI:

https://boris.unibe.ch/id/eprint/126390

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