These authors contributed equally to this study.
RNF43 is a tumour suppressor gene mutated in mucinous tumours of the ovary
Article first published online: 25 JAN 2013
Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 229, Issue 3, pages 469–476, February 2013
How to Cite
Ryland, G. L., Hunter, S. M., Doyle, M. A., Rowley, S. M., Christie, M., Allan, P. E., Bowtell, D. D., Australian Ovarian Cancer Study Group,, Gorringe, K. L. and Campbell, I. G. (2013), RNF43 is a tumour suppressor gene mutated in mucinous tumours of the ovary. J. Pathol., 229: 469–476. doi: 10.1002/path.4134
No conflicts of interest were declared.
- Issue published online: 25 JAN 2013
- Article first published online: 25 JAN 2013
- Accepted manuscript online: 24 OCT 2012 03:03AM EST
- Manuscript Accepted: 7 OCT 2012
- Manuscript Revised: 20 SEP 2012
- Manuscript Received: 25 AUG 2012
- mucinous ovarian cancer;
- somatic mutation;
- DNA sequencing
Mucinous carcinomas represent a distinct morphological subtype which can arise from several organ sites, including the ovary, and their genetic characteristics are largely under-described. Exome sequencing of 12 primary mucinous ovarian tumours identified RNF43 as the most frequently somatically mutated novel gene, secondary to KRAS and mutated at a frequency equal to that of TP53 and BRAF. Further screening of RNF43 in a larger cohort of ovarian tumours identified additional mutations, with a total frequency of 2/22 (9%) in mucinous ovarian borderline tumours and 6/29 (21%) in mucinous ovarian carcinomas. Seven mutations were predicted to truncate the protein and one missense mutation was predicted to be deleterious by in silico analysis. Six tumours had allelic imbalance at the RNF43 locus, with loss of the wild-type allele. The mutation spectrum strongly suggests that RNF43 is an important tumour suppressor gene in mucinous ovarian tumours, similar to its reported role in mucinous pancreatic precancerous cysts. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.