Litchfield, K, Levy, M, Dudakia, D et al. (13 more authors) (2016) Rare disruptive mutations in ciliary function genes contribute to testicular cancer susceptibility. Nature Communications, 7. 13840. ISSN 2041-1723
Abstract
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 by a dnaaf1hu²⁵⁵h(+/−) zebrafish model, which has a 94% risk of TGCT. Our data implicate cilia-microtubule inactivation as a cause of TGCT and provide evidence for CMGs as cancer susceptibility genes.
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Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2016, The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Epidemiology and Biostatistics (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 24 Jan 2017 16:23 |
Last Modified: | 05 Oct 2017 16:26 |
Published Version: | https://doi.org/10.1038/ncomms13840 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/ncomms13840 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:111033 |