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MYC oncogene elicits tumorigenesis associated with embryonic, ribosomal biogenesis, and tissue-lineage dedifferentiation gene expression changes

Sullivan, Delaney K. and Deutzmann, Anja and Yarbrough, Josiah and Krishnan, Maya S. and Gouw, Arvin M. and Bellovin, David I. and Adam, Stacey J. and Liefwalker, Daniel F. and Dhanasekaran, Renumathy and Felsher, Dean W. (2022) MYC oncogene elicits tumorigenesis associated with embryonic, ribosomal biogenesis, and tissue-lineage dedifferentiation gene expression changes. Oncogene, 41 . pp. 4960-4970. ISSN 0950-9232. doi:10.1038/s41388-022-02458-9.

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MYC is a transcription factor frequently overexpressed in cancer. To determine how MYC drives the neoplastic phenotype, we performed transcriptomic analysis using a panel of MYC-driven autochthonous transgenic mouse models. We found that MYC elicited gene expression changes mostly in a tissue- and lineage-specific manner across B-cell lymphoma, T-cell acute lymphoblastic lymphoma, hepatocellular carcinoma, renal cell carcinoma, and lung adenocarcinoma. However, despite these gene expression changes being mostly tissue-specific, we uncovered a convergence on a common pattern of upregulation of embryonic stem cell gene programs and downregulation of tissue-of-origin gene programs across MYC-driven cancers. These changes are representative of lineage dedifferentiation, that may be facilitated by epigenetic alterations that occur during tumorigenesis. Moreover, while several cellular processes are represented among embryonic stem cell genes, ribosome biogenesis is most specifically associated with MYC expression in human primary cancers. Altogether, MYC’s capability to drive tumorigenesis in diverse tissue types appears to be related to its ability to both drive a core signature of embryonic genes that includes ribosomal biogenesis genes as well as promote tissue and lineage specific dedifferentiation.

Item Type:Article
Related URLs:
URLURL TypeDescription ReadCube access
Sullivan, Delaney K.0000-0002-8359-6705
Deutzmann, Anja0000-0002-3271-1427
Yarbrough, Josiah0000-0002-4521-0656
Gouw, Arvin M.0000-0002-9552-635X
Adam, Stacey J.0000-0002-4590-5175
Dhanasekaran, Renumathy0000-0001-8819-7511
Felsher, Dean W.0000-0003-2496-523X
Additional Information:We thank Andrew J. Gentles and Felsher laboratory members for their advice and guidance. We thank Stanford Research Computing Center for computational resources, including the Sherlock cluster. We are grateful for the public data from TCGA and from the Broad Institute’s CCLE. This work was funded by National Institutes of Health (NIH) grants: R35 CA253180, R01 CA089305, R01 CA170378, and U01 CA188383, with additional support as follows. DKS - UCLA-Caltech Medical Scientist Training Program (NIH NIGMS training grant T32 GM008042). AD - Lymphoma Research Foundation. RD - NIH grant CA222676 from the National Cancer Institute (NCI), American College of Gastroenterology Junior Faculty Career Development Grant. AMG - Stanford Cancer Translational Nanotechnology Training T32 Training Grant CA196585 (NCI). DFL - Tumor Biology Training Grant (NIH 5T32CA009151-38), Stanford University (NCI), Burroughs Wellcome Fund Postdoctoral Enrichment Award, Research Supplement Award (NCI), 3U01CA188383-03S1, and (K01) CA234453 (NCI). Code availability. For transparency of methods, all the code and procedures that can be used to reproduce the results in this paper, starting from the raw data, are available at and the relevant data from all public datasets used in this study (e.g., TCGA, CCLE, dbSUPER, etc.) are also accessible via this repository.
Funding AgencyGrant Number
NIHR35 CA253180
NIHR01 CA089305
NIHR01 CA170378
NIHU01 CA188383
NIH Predoctoral FellowshipT32 GM008042
Lymphoma Research FoundationUNSPECIFIED
American College of GastroenterologyUNSPECIFIED
NIH Predoctoral FellowshipT32 CA196585
NIH Predoctoral Fellowship5T32CA009151-38
Stanford UniversityUNSPECIFIED
Burroughs Wellcome FundUNSPECIFIED
NIHK01 CA234453
Record Number:CaltechAUTHORS:20221017-15547800.41
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ID Code:117476
Deposited By: Research Services Depository
Deposited On:25 Oct 2022 19:03
Last Modified:08 Nov 2022 00:13

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