TY - JOUR
T1 - Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
AU - Schaub, Franz X.
AU - Dhankani, Varsha
AU - Berger, Ashton C.
AU - Trivedi, Mihir
AU - Richardson, Anne B.
AU - Shaw, Reid
AU - Zhao, Wei
AU - Zhang, Xiaoyang
AU - Ventura, Andrea
AU - Liu, Yuexin
AU - Ayer, Donald E.
AU - Hurlin, Peter J.
AU - Cherniack, Andrew D.
AU - Eisenman, Robert N.
AU - Bernard, Brady
AU - Grandori, Carla
AU - Caesar-Johnson, Samantha J.
AU - Demchok, John A.
AU - Felau, Ina
AU - Kasapi, Melpomeni
AU - Ferguson, Martin L.
AU - Hutter, Carolyn M.
AU - Sofia, Heidi J.
AU - Tarnuzzer, Roy
AU - Wang, Zhining
AU - Yang, Liming
AU - Zenklusen, Jean C.
AU - Zhang, Jiashan (Julia)
AU - Chudamani, Sudha
AU - Liu, Jia
AU - Lolla, Laxmi
AU - Naresh, Rashi
AU - Pihl, Todd
AU - Sun, Qiang
AU - Wan, Yunhu
AU - Wu, Ye
AU - Cho, Juok
AU - DeFreitas, Timothy
AU - Frazer, Scott
AU - Gehlenborg, Nils
AU - Getz, Gad
AU - Heiman, David I.
AU - Kim, Jaegil
AU - Lawrence, Michael S.
AU - Lin, Pei
AU - Meier, Sam
AU - Noble, Michael S.
AU - Saksena, Gordon
AU - Voet, Doug
AU - Mann, Graham
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/3/28
Y1 - 2018/3/28
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.
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. 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.
KW - MAX
KW - MNT
KW - MYC genomic alterations
KW - TCGA
KW - The Cancer Genome Atlas
UR - http://www.scopus.com/inward/record.url?scp=85044336302&partnerID=8YFLogxK
U2 - 10.1016/j.cels.2018.03.003
DO - 10.1016/j.cels.2018.03.003
M3 - Article
SN - 2405-4712
VL - 6
SP - 282-300.e2
JO - Cell Systems
JF - Cell Systems
IS - 3
ER -