Journal
JOURNAL OF MEDICAL GENETICS
Volume 58, Issue 9, Pages 581-585Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/jmedgenet-2020-107087
Keywords
child health; cytogenetics; genetic predisposition to disease; genetics; germ-line mutation
Categories
Funding
- Manchester NIHR Biomedical Research Centre [IS-BRC-1215-20007]
- European Research Council
- NIHR
- Cambridge NIHR Biomedical Research Centre
- Cancer Research UK Cambridge Cancer Centre
- Wellcome Trust
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The role of constitutional deletion CNVs in nephroblastomatosis is highlighted in this study, with a particular focus on a delCNV encompassing the REST tumor suppressor gene. Deletion studies involving known cancer predisposition genes can provide insights into the relationship between genomic architecture and associated tumor risk.
Background Nephroblastomatosis is a recognised precursor for the development of Wilms tumour (WT), the most common childhood renal tumour. While the majority of WT is sporadic in origin, germline intragenic mutations of predisposition genes such as WT1, REST and TRIM28 have been described in apparently isolated (non-familial) WT. Despite constitutional CNVs being a well-studied cause of developmental disorders, their role in cancer predisposition is less well defined, so that the interpretation of cancer risks associated with specific CNVs can be complex. Objective To highlight the role of a constitutional deletion CNV (delCNV) encompassing the REST tumour suppressor gene in diffuse hyperplastic perilobar nephroblastomatosis (HPLN). Methods/results Array comparative genomic hybridisation in an infant presenting with apparently sporadic diffuse HPLN revealed a de novo germline CNV, arr[GRCh37] 4q12(57,385,330-57,947,405)x1. The REST tumour suppressor gene is located at GRCh37 chr4:57,774,042-57,802,010. Conclusion This delCNV encompassing REST is associated with nephroblastomatosis. Deletion studies should be included in the molecular work-up of inherited predisposition to WT/nephroblastomatosis. Detection of delCNVs involving known cancer predisposition genes can yield insights into the relationship between underlying genomic architecture and associated tumour risk.
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