Clinically and biologically relevant subgroups of Wilms tumour defined by genomic and epigenomic analyses.

Clinically and biologically relevant subgroups of Wilms tumour defined by genomic and epigenomic analyses.:

Clinically and biologically relevant subgroups of Wilms tumour defined by genomic and epigenomic analyses.

Br J Cancer. 2020 Oct 05;:

Authors: Brzezinski J, Choufani S, Romao R, Shuman C, Chen H, Cunanan J, Bagli D, Grant R, Lorenzo A, Weksberg R

Abstract

BACKGROUND: Although cure rates for Wilms tumours (WT) are high, many patients receive therapy with attendant long-term complications. Our goal was to stratify WT using genome-wide analyses to identify candidate molecular features for patients who would benefit from a reduction in therapy.

METHODS: We generated DNA methylation and exome sequencing data on WT-kidney pairs (n = 57) and unpaired tumours (n = 27) collected either at our centre or by the Children's Oncology Group. Samples were divided into a discovery set (n = 32) and validation set (n = 52).

RESULTS: Analysis of DNA methylation revealed two subgroups of WT with distinct features. Subgroup A has a similar DNA methylation profile to mature kidney, while Subgroup B has genome-wide dysregulation of DNA methylation. The rate of non-synonymous missense mutations and segmental chromosomal aberrations was higher in Subgroup B tumours, suggesting that this group has genome instability related to its epigenetic state. Subgroup A had a higher proportion of cases of bilateral disease. Tumours with high-risk histology or from patients who relapsed were only found in Subgroup B.

CONCLUSION: We have identified subgroup-specific molecular events that could inform future work supporting more targeted therapeutic approaches and patient stratification. We propose a novel developmental tumour model based on these findings.



PMID: 33012783 [PubMed - as supplied by publisher]