Journal
NATURE GENETICS
Volume 49, Issue 7, Pages 1133-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3896
Keywords
-
Categories
Funding
- National Health Service
- US National Institutes of Health (NIH) [U19 CA 148537, X01HG007492, HHSN268201200008I]
- NIH NCI [U01 CA188392]
- Cancer Research UK [C5047/A7357, C1287/A10118, C1287/A16563, C5047/A3354, C5047/A10692, C16913/A6135, C1298/A8362]
- European Commission [223175 (HEALTH-F2-2009-223175)]
- NIH Cancer Post-Cancer GWAS initiative grant [1 U19 CA 148537-01]
- Institute of Cancer Research
- Everyman Campaign
- Prostate Cancer Research Foundation
- Prostate Action
- Orchid Cancer Appeal
- National Cancer Research Network UK
- National Cancer Research Institute (NCRI) UK
- NIHR
- Royal Marsden NHS Foundation Trust
- Swedish Cancer Society [CAN2011/484, CAN2012/823]
- Norwegian Cancer Society [418975-71081-PR-2006-0387, PK01-20070375]
- Nordic Cancer Union [S-12/07]
- Movember Foundation
- Cancer Research UK
- MRC [MR/N01104X/1, MR/N01104X/2, G1001799, G0700491] Funding Source: UKRI
- Cancer Research UK [10589, 10118, 19167, 13065, 16563, 17528, 15007] Funding Source: researchfish
- Medical Research Council [MR/N01104X/2, G1001799, MR/N01104X/1, G0700491] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10096] Funding Source: researchfish
Ask authors/readers for more resources
Genome-wide association studies (GWAS) have transformed understanding of susceptibility to testicular germ cell tumors (TGCTs), but much of the heritability remains unexplained. Here we report a new GWAS, a meta-analysis with previous GWAS and a replication series, totaling 7,319 TGCT cases and 23,082 controls. We identify 19 new TGCT risk loci, roughly doubling the number of known TGCT risk loci to 44. By performing in situ Hi-C in TGCT cells, we provide evidence for a network of physical interactions among all 44 TGCT risk SNPs and candidate causal genes. Our findings implicate widespread disruption of developmental transcriptional regulators as a basis of TGCT susceptibility, consistent with failed primordial germ cell differentiation as an initiating step in oncogenesis(1). Defective microtubule assembly and dysregulation of KIT-MAPK signaling also feature as recurrently disrupted pathways. Our findings support a polygenic model of risk and provide insight into the biological basis of TGCT.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available