RUNX1 is a driver of renal cell carcinoma correlating with clinical outcome

Rooney, N. et al. (2020) RUNX1 is a driver of renal cell carcinoma correlating with clinical outcome. Cancer Research, 80(11), pp. 2325-2339. (doi: 10.1158/0008-5472.CAN-19-3870) (PMID:32156779)

Abstract

The recurring association of specific genetic lesions with particular types of cancer is a fascinating, and largely unexplained area of cancer biology. This is particularly true of clear cell renal cell carcinoma (ccRCC) where although key mutations such as loss of VHL is an almost ubiquitous finding, there remains a conspicuous lack of targetable genetic drivers. In this study, we have identified a previously unknown pro-tumorigenic role for the RUNX genes in this disease setting. Analysis of patient tumor biopsies together with loss of function studies in preclinical models established the importance of RUNX1 and RUNX2 in ccRCC. Patients with high RUNX1 (and RUNX2) expression exhibited significantly poorer clinical survival compared to patients with low expression. This was functionally relevant as deletion of RUNX1 in ccRCC cell lines reduced tumor cell growth and viability in vitro and in vivo. Transcriptional profiling of RUNX1-CRISPR-deleted cells revealed a gene signature dominated by extracellular matrix remodelling, notably affecting STMN3, SERPINH1, and EPHRIN signaling. Finally, RUNX1 deletion in a genetic mouse model of kidney cancer improved overall survival and reduced tumor cell proliferation. In summary, these data attest to the validity of targeting a RUNX1-transcriptional program in ccRCC. [Abstract copyright: Copyright ©2020, American Association for Cancer Research.]

• Item Type: Articles
• Additional Information: This work 577 was funded by CRUK core funding C596/A17196 (KB and OJS labs - CRUK Beatson Institute) and 578 Renal Cancer Research Fund Scotland (to JE) who supported the TMA production.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Leach, Dr Joshua and Nixon, Mr Colin and Clark, Mr William and Campbell, Dr Kirsteen and Blyth, Professor Karen and Athineos, Mr Dimitris and Däbritz, Jan and Cameron, Professor Ewan and Edwards, Professor Joanne and Mason, Miss Susan and Sansom, Professor Owen
• Authors: Rooney, N., Mason, S. M., McDonald, L., Däbritz, J. H. M., Campbell, K. J., Hedley, A., Howard, S., Athineos, D., Nixon, C., Clark, W., Leach, J. D., Sansom, O. J., Edwards, J., Cameron, E. R., and Blyth, K.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Cancer Research
• Publisher: American Association for Cancer Research
• ISSN: 0008-5472
• ISSN (Online): 1538-7445
• Published Online: 10 March 2020
• Copyright Holders: Copyright ©2020, American Association for Cancer Research
• First Published: First published in Cancer Research 80 (11):2325-2339
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher