Analysis of the DND1 gene in men with sporadic and familial testicular germ cell tumors.
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.
Linger
Rachel
R
Testicular Cancer Genetics Team, Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
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
D004252:DNA Mutational Analysis; D005192:Family Health; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009373:Neoplasms, Germ Cell and Embryonal / Q000209:etiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D013736:Testicular Neoplasms / Q000209:etiology / Q000235:genetics*
C528453:Dnd1 protein, human; D009363:Neoplasm Proteins