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Analysis of the DND1 gene in men with sporadic and familial testicular germ cell tumors
Author(s) -
Linger Rachel,
Dudakia Darshna,
Huddart Robert,
Tucker Kathy,
Friedlander Michael,
Phillips KellyAnne,
Hogg David,
Jewett Michael A. S.,
Lohynska Radka,
Daugaard Gedske,
Richard Stéphane,
Chompret Agnes,
StoppaLyonnet Dominique,
BonaïtiPellié Catherine,
Heidenreich Axel,
Albers Peter,
Olah Edith,
Geczi Lajos,
Bodrogi Istvan,
Daly Peter A.,
Guilford Parry,
Fosså Sophie D.,
Heimdal Ketil,
Tjulandin Sergei A.,
Liubchenko Ludmila,
Stoll Hans,
Weber Walter,
Einhorn Lawrence,
McMaster Mary,
Korde Larissa,
Greene Mark H.,
Nathanson Katherine L.,
Cortessis Victoria,
Easton Douglas F.,
Bishop D. Timothy,
Stratton Michael R.,
Rapley Elizabeth A.
Publication year - 2008
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20526
Subject(s) - gene , genetics , biology , germ cell , testicular germ cell tumor , germ cell tumors , family history , testicular cancer , cancer , medicine , chemotherapy
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 additional 842 index TGCT cases (269 with a family history of TGCT and 573 without) did not reveal any additional instances. The variant, p. Glu86Ala, is within a known functional domain of DND1 and is highly conserved through evolution. Although the variant may be a rare polymorphism, a change at such a highly conserved residue is characteristic of a disease‐causing variant. Whether it is disease‐causing or not, mutations in DND1 make, at most, a very small contribution to TGCT susceptibility in adults and adolescents. © 2007 Wiley‐Liss, Inc.