Identification of 19 novel loci reveals gene regulatory mechanisms determining susceptibility to testicular germ cell tumour

Study ID Alternative Stable ID Type
EGAS00001001836 Other

Study Description

Testicular germ cell tumour (TGCT) is the most common cancer in young men1,2, and is characterised by strong inherited genetic risk factors3. Here we have undertaken large-scale genome wide association study (GWAS) for TGCT, encompassing ~7,500 cases and ~23,000 controls, through the Oncoarray consortium. We identified 19 novel loci, approximately doubling the number of known TGCT risk loci to 44 (P<5x10-8)4-14 and conduct deep, high-throughput functional annotation of all risk loci. We establish a network of physical interactions for all risk SNPs to candidate casual genes in 3D space, using high-throughput chromosome conformation capture techniques (HiC) in TGCT cells. Firstly, functional evidence reveals widespread disruption of developmental transcriptional regulators, consistent with failed primordial germ cell differentiation as an initiating step in TGCT oncogenesis15. We secondly observe multiple risk loci associated with defective microtubule assembly, compatible with the high level of aneuploidy observed in TGCTs, suggesting gross chromosomal instability. Finally ... (Show More)

Study Datasets 2 datasets.

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Dataset ID Description Technology Samples
UK TGCT controls samples using theInfinium OncoArray-500K BeadChip
Infinium OncoArray-500K BeadChip 7422
UK TGCT case samples using theInfinium OncoArray-500K BeadChip
Infinium OncoArray-500K BeadChip 3206

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