Analysis of the DND1 gene in men with sporadic and familial testicular germ cell tumors.
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ABSTRACT:
SUBMITTER: Linger R
PROVIDER: S-EPMC3109865 | biostudies-literature | 2008 Mar
REPOSITORIES: biostudies-literature
Publications
Analysis of the DND1 gene in men with sporadic and familial testicular germ cell tumors.
Linger Rachel R Dudakia Darshna D Huddart Robert R Tucker Kathy K Friedlander Michael M Phillips Kelly-Anne KA Hogg David D Jewett Michael A S MA Lohynska Radka R Daugaard Gedske G Richard Stéphane S Chompret Agnes A Stoppa-Lyonnet Dominique D Bonaïti-Pellié Catherine C Heidenreich Axel A Albers Peter P Olah Edith E Geczi Lajos L Bodrogi Istvan I Daly Peter A PA Guilford Parry P Fosså Sophie D SD Heimdal Ketil K Tjulandin Sergei A SA Liubchenko Ludmila L Stoll Hans H Weber Walter W Einhorn Lawrence L McMaster Mary M Korde Larissa L Greene Mark H MH Nathanson Katherine L KL Cortessis Victoria V Easton Douglas F DF Bishop D Timothy DT Stratton Michael R MR Rapley Elizabeth A EA
Genes, chromosomes & cancer 20080301 3
A base substitution in the mouse Dnd1 gene resulting in a truncated Dnd protein has been shown to be responsible for germ cell loss and the development of testicular germ cell tumors (TGCT) in the 129 strain of mice. We investigated the human orthologue of this gene in 263 patients (165 with a family history of TGCT and 98 without) and found a rare heterozygous variant, p. Glu86Ala, in a single case. This variant was not present in control chromosomes (0/4,132). Analysis of the variant in an add ...[more]
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Project description:BackgroundTesticular germ cell tumor (TGCT) is the most common malignancy in young men. Familial clustering, epidemiologic evidence of increased risk with family or personal history, and the association of TGCT with genitourinary (GU) tract anomalies have suggested an underlying genetic predisposition. Linkage data have not identified a rare, highly-penetrant, single gene in familial TGCT (FTGCT) cases. Based on its association with congenital GU tract anomalies and suggestions that there is an intrauterine origin to TGCT, we hypothesized the existence of unrecognized dysmorphic features in FTGCT.MethodsWe evaluated 38 FTGCT individuals and 41 first-degree relatives from 22 multiple-case families with detailed dysmorphology examinations, physician-based medical history and physical examination, laboratory testing, and genitourinary imaging studies.ResultsThe prevalence of major abnormalities and minor variants did not significantly differ between either FTGCT individuals or their first-degree relatives when compared with normal population controls, except for tall stature, macrocephaly, flat midface, and retro-/micrognathia. However, these four traits were not manifest as a constellation of features in any one individual or family. We did detect an excess prevalence of the genitourinary anomalies cryptorchidism and congenital inguinal hernia in our population, as previously described in sporadic TGCT, but no congenital renal, retroperitoneal or mediastinal anomalies were detected.ConclusionsOverall, our study did not identify a constellation of dysmorphic features in FTGCT individuals, which is consistent with results of genetic studies suggesting that multiple low-penetrance genes are likely responsible for FTGCT susceptibility.
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