Next Article in Journal
Overexpression of MiR482c in Tomato Induces Enhanced Susceptibility to Late Blight
Next Article in Special Issue
Characterizing CDK8/19 Inhibitors through a NFκB-Dependent Cell-Based Assay
Previous Article in Journal
Protective to a T: The Role of T Cells during Zika Virus Infection

Identifying Cancers Impacted by CDK8/19

Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC 29208, USA
Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia
MTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Hungarian Academy of Sciences, Magyar tudósok körútja 2., H-1117 Budapest, Hungary
Department of Pediatrics, Semmelweis University, Tűzoltó utca 7-9, H-1094 Budapest, Hungary
Blokhin National Medical Research Center of Oncology, 115478 Moscow, Russia
Author to whom correspondence should be addressed.
Academic Editor: Yubin Ge
Cells 2019, 8(8), 821;
Received: 29 June 2019 / Revised: 19 July 2019 / Accepted: 29 July 2019 / Published: 3 August 2019
(This article belongs to the Special Issue The Role of Mediator Kinase in Cancer )
CDK8 and CDK19 Mediator kinases are transcriptional co-regulators implicated in several types of cancer. Small-molecule CDK8/19 inhibitors have recently entered or are entering clinical trials, starting with breast cancer and acute myeloid leukemia (AML). To identify other cancers where these novel drugs may provide benefit, we queried genomic and transcriptomic databases for potential impact of CDK8, CDK19, or their binding partner CCNC. sgRNA analysis of a panel of tumor cell lines showed that most tumor types represented in the panel, except for some central nervous system tumors, were not dependent on these genes. In contrast, analysis of clinical samples for alterations in these genes revealed a high frequency of gene amplification in two highly aggressive subtypes of prostate cancer and in some cancers of the GI tract, breast, bladder, and sarcomas. Analysis of survival correlations identified a group of cancers where CDK8 expression correlated with shorter survival (notably breast, prostate, cervical cancers, and esophageal adenocarcinoma). In some cancers (AML, melanoma, ovarian, and others), such correlations were limited to samples with a below-median tumor mutation burden. These results suggest that Mediator kinases are especially important in cancers that are driven primarily by transcriptional rather than mutational changes and warrant an investigation of their role in additional cancer types. View Full-Text
Keywords: CDK8; CDK19; Cyclin C; cancer genomics; survival correlations CDK8; CDK19; Cyclin C; cancer genomics; survival correlations
Show Figures

Figure 1

MDPI and ACS Style

Roninson, I.B.; Győrffy, B.; Mack, Z.T.; Shtil, A.A.; Shtutman, M.S.; Chen, M.; Broude, E.V. Identifying Cancers Impacted by CDK8/19. Cells 2019, 8, 821.

AMA Style

Roninson IB, Győrffy B, Mack ZT, Shtil AA, Shtutman MS, Chen M, Broude EV. Identifying Cancers Impacted by CDK8/19. Cells. 2019; 8(8):821.

Chicago/Turabian Style

Roninson, Igor B., Balázs Győrffy, Zachary T. Mack, Alexander A. Shtil, Michael S. Shtutman, Mengqian Chen, and Eugenia V. Broude. 2019. "Identifying Cancers Impacted by CDK8/19" Cells 8, no. 8: 821.

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Back to TopTop