Next Article in Journal
Overexpression of MiR482c in Tomato Induces Enhanced Susceptibility to Late Blight
Previous Article in Journal
Protective to a T: The Role of T Cells during Zika Virus Infection
Open AccessArticle

Identifying Cancers Impacted by CDK8/19

1
Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC 29208, USA
2
Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia
3
MTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Hungarian Academy of Sciences, Magyar tudósok körútja 2., H-1117 Budapest, Hungary
4
Department of Pediatrics, Semmelweis University, Tűzoltó utca 7-9, H-1094 Budapest, Hungary
5
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; https://doi.org/10.3390/cells8080821
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 )
  |  
PDF [4657 KB, uploaded 3 August 2019]
  |  

Abstract

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
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

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.

Show more citation formats Show less citations formats

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

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cells EISSN 2073-4409 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top