Journal article
Rare germline copy number deletions of likely functional importance are implicated in endometrial cancer predisposition
Human Genetics, Vol.134(3), pp.269-278
2015
Abstract
Endometrial cancer is the most common invasive gynaecological cancer in women, and relatively little is known about inherited risk factors for this disease. This is the first genome-wide study to explore the role of common and rare germline copy number variants (CNVs) in predisposition to endometrial cancer. CNVs were called from germline DNA of 1,209 endometrioid endometrial cancer cases and 528 cancer-unaffected female controls. Overall CNV load of deletions or DNA gains did not differ significantly between cases and controls (P > 0.05), but cases presented with an excess of rare germline deletions overlapping likely functional genomic regions including genes (P = 8 × 10-10), CpG islands (P = 1 × 10-7) and sno/miRNAs regions (P = 3 × 10-9). On average, at least one additional gene and two additional CpG islands were disrupted by rare deletions in cases compared to controls. The most pronounced difference was that over 30 sno/miRNAs were disrupted by rare deletions in cases for every single disruption event in controls. A total of 13 DNA repair genes were disrupted by rare deletions in 19/1,209 cases (1.6 %) compared to one gene in 1/528 controls (0.2 %; P = 0.007), and this increased DNA repair gene loss in cases persisted after excluding five individuals carrying CNVs disrupting mismatch repair genes MLH1, MSH2 and MSH6 (P = 0.03). There were 34 miRNA regions deleted in at least one case but not in controls, the most frequent of which encompassed hsa-mir-661 and hsa-mir-203. Our study implicates rare germline deletions of functional and regulatory regions as possible mechanisms conferring endometrial cancer risk, and has identified specific regulatory elements as candidates for further investigation. © 2014, Springer-Verlag Berlin Heidelberg.
Details
- Title
- Rare germline copy number deletions of likely functional importance are implicated in endometrial cancer predisposition
- Authors
- G L Moir-Meyer (Author) - University of Otago, New ZealandJ F Pearson (Author) - University of Otago, New ZealandFelicity Lose (Author) - Queensland Institute of Medical ResearchR J Scott (Author) - University of NewcastleM McEvoy (Author) - University of NewcastleJ Attia (Author) - University of NewcastleE G Holliday (Author) - Hunter Medical Research InstituteP D Pharoah (Author) - University of Cambridge, United KingdomA M Dunning (Author) - University of Cambridge, United KingdomD J Thompson (Author) - University of Cambridge, United KingdomD F Easton (Author) - University of Cambridge, United KingdomA B Spurdle (Author) - Queensland Institute of Medical ResearchL C Walker (Author) - University of Otago, New Zealand
- Publication details
- Human Genetics, Vol.134(3), pp.269-278
- Publisher
- Springer
- Date published
- 2015
- DOI
- 10.1007/s00439-014-1507-4
- ISSN
- 0340-6717
- Organisation Unit
- University of the Sunshine Coast, Queensland; Office of Research
- Language
- English
- Record Identifier
- 99450475902621
- Output Type
- Journal article
Metrics
494 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Web Of Science research areas
- Genetics & Heredity
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites