No conflicts of interest were declared.
Oncogenic NRF2 mutations in squamous cell carcinomas of oesophagus and skin†
Version of Record online: 22 OCT 2009
Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 220, Issue 4, pages 446–451, March 2010
How to Cite
Kim, Y. R., Oh, J. E., Kim, M. S., Kang, M. R., Park, S. W., Han, J. Y., Eom, H. S., Yoo, N. J. and Lee, S. H. (2010), Oncogenic NRF2 mutations in squamous cell carcinomas of oesophagus and skin. J. Pathol., 220: 446–451. doi: 10.1002/path.2653
- Issue online: 5 FEB 2010
- Version of Record online: 22 OCT 2009
- Accepted manuscript online: 22 OCT 2009 12:00AM EST
- Manuscript Accepted: 12 OCT 2009
- Manuscript Revised: 25 SEP 2009
- Manuscript Received: 11 AUG 2009
- National Cancer Control R&D Program. Grant Number: 0820080
- oesophageal cancer;
- squamous cell carcinoma
Nuclear factor erythroid-related factor 2 (NRF2) encodes a transcription factor that induces expression of cytoprotective proteins upon oxidative stress and oncogenic NRF2 mutations have been found in lung and head/neck cancers that inactivate KEAP1-mediated degradation of NRF2. The aim of this study was to catalogue NRF2 mutations in other human cancers. For this, we analysed 1145 cancer tissues from carcinomas from oesophagus, skin, uterine cervix, lung, larynx, breast, colon, stomach, liver, prostate, urinary bladder, ovary, uterine cervix, and kidney, and meningiomas, multiple myelomas, and acute leukaemias by single-strand conformation polymorphism (SSCP) assay. We detected NRF2 mutations in oesophagus (8/70; 11.4%), skin (1/17; 6.3%), lung (10/125; 8.0%), and larynx (3/23; 13.0%) cancers. Of note, all of the 22 mutations except one were found in squamous cell carcinomas (SCCs) (95.5%). The mutations were observed within or near DLG and ETGE motifs that are important in NRF2 and KEAP1 interaction. All of the oesophageal SCCs and skin SCCs with the NRF2 mutations showed increased NRF2 expression in the nuclei. However, none of the SCCs from oesophagus and skin harboured KEAP1 mutation. Our study demonstrated here that NRF2 mutation occurs not only in lung and head/neck cancers, but also in oesophageal and skin cancers. Our data suggest that the NRF2 mutation plays a role in the development of SCC and is a feature of SCC. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.