Clinically and biologically relevant subgroups of Wilms tumour defined by genomic and epigenomic analyses
| Autor: | Rodrigo Romao, Darius J. Bägli, Joanna Cunanan, Armando J. Lorenzo, Ronald Grant, Haiying Chen, Rosanna Weksberg, Cheryl Shuman, Jack Brzezinski, Sanaa Choufani |
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| Rok vydání: | 2020 |
| Předmět: |
Epigenomics
Male Genome instability Oncology Cancer Research medicine.medical_specialty Genes Wilms Tumor Wilms tumour Wilms Tumor Article Paediatric cancer Prognostic markers 03 medical and health sciences 0302 clinical medicine Internal medicine Exome Sequencing Cancer genomics Humans Medicine Missense mutation Epigenetics Child Exome sequencing Chromosome Aberrations business.industry Gene Expression Profiling Histology DNA Methylation Kidney Neoplasms 030220 oncology & carcinogenesis Mutation DNA methylation Female business |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/s41416-020-01102-1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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