Rare disruptive mutations in ciliary function genes contribute to testicular cancer susceptibility
- Litchfield, K
- Levy, M
- Dudakia, D
- Proszek, P
- Shipley, C
- Basten, S
- Rapley, E
- Bishop, DT
- Reid, A
- Huddart, R
- Broderick, P
- Gonzalez de Castro, D
- O'Connor, S
- Giles, RH
- Houlston, RS
- Turnbull, C
DOIAbstract
Testicular germ cell tumour (TGCT) is the most common cancer in young men. Here we sought to identify risk factors for TGCT by performing whole-exome sequencing on 328 TGCT cases from 153 families, 634 sporadic TGCT cases and 1,644 controls. We search for genes that are recurrently affected by rare variants (minor allele frequency <0.01) with potentially damaging effects and evidence of segregation in families. A total of 8.7% of TGCT families carry rare disruptive mutations in the cilia-microtubule genes (CMG) as compared with 0.5% of controls (P=2.1 × 10¯⁸). The most significantly mutated CMG is DNAAF1 with biallelic inactivation and loss of DNAAF1 expression shown in tumours from carriers. DNAAF1 mutation as a cause of TGCT is supported ...
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