Large-scale Sequencing of Testicular Germ Cell Tumour (TGCT) Cases Excludes Major TGCT Predisposition Gene

Publication date: June 2018 Source:European Urology, Volume 73, Issue 6 Author(s): Kevin Litchfield, Chey Loveday, Max Levy, Darshna Dudakia, Elizabeth Rapley, Jeremie Nsengimana, D. Tim Bishop, Alison Reid, Robert Huddart, Peter Broderick, Richard S. Houlston, Clare Turnbull Testicular germ cell tumour (TGCT), the most common cancer in young men, has a significant heritable basis that has long raised questions as to the existence of underlying major high-penetrance susceptibility gene(s). To determine the contribution of rare gene mutations to the inherited risk of TGCT, we analysed germline whole-exome data for 919 TGCT cases and 1609 cancer-free controls. We compared frequencies between TGCT cases and controls of rare (<1%) and low-frequency (1-5%) coding variants (1) individually and (2) collapsed at the gene level via burden testing (T1, disruptive; T2, all deleterious; and T3, all nonsynonymous) using Fisher's exact test with Bonferroni correction of significance thresholds. No individual variant or individual gene showed a significant association with TGCT after correction for multiple testing. In the largest whole-exome sequencing study of testicular cancer reported to date, our findings do not support the existence of a major high-penetrance TGCT susceptibility gene (of odds ratio >10 and allele frequency [combined]>0.01%). Owing to its power, this study cannot exclude the existence of susceptibility genes responsible for occasional...
Source: European Urology - Category: Urology & Nephrology Source Type: research