Document Type
Journal Article
Publication Date
10-2014
Journal
PLoS ONE
Volume
Volume 9, Issue 10
Inclusive Pages
Article number e109924
DOI
10.1371/journal.pone.0109924
Keywords
Kidney--pathology; Kidney Neoplasms--genetics; Neoplasm Recurrence, Local--genetics; Tumor Markers, Biological--genetics; Tumor Suppressor Protein p53--genetics; Wilms Tumor--genetics
Abstract
Purpose
The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whetherTP53 mutational status confers additional prognostic information.
Patients and Methods
We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling.
Results
From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26–16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36–31.7) compared to tumours lackingTP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes.
Conclusion
This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Maschietto, M., Williams, R.D., Chagtai, T., Popov, S.D., Sebire, N.J. et al. (2014). TPS mutational status is a potential marker for risk stratification in Wilms tumour with diffuse anaplasia. PLoS ONE, 9(10): e109924.
Peer Reviewed
1
Open Access
1
Comments
Reproduced with permission of PLoS ONE.