title: Screening for germline DND1 mutations in testicular cancer patients.
abstract: Although several observations suggest that a strong genetic predisposition to developing testicular germ cell tumors (TGCT) exists, no associated, highly penetrant germline mutations have been identified so far. In the 129/Sv mouse strain, a germline mutation in the DND1 gene has been shown to strongly increase the TGCT risk. We screened 272 men with TGCT (89% sporadic cases, 11% familial) for germline mutations in the human homologue of DND1. A single nucleotide substitution c.657C > G (p.Asp219Glu) was observed in a non-familial case of testicular embryonal carcinoma. The variant was also present in the patient's asymptomatic father and two brothers, but not observed in 210 control chromosomes. The wild type DND1 allele was not lost in the patient's tumor. In silico analysis of the variant predicts it to be non-pathogenic. We conclude that germline DND1 mutations are unlikely to contribute significantly to human testicular germ cell tumor susceptibility. The role of human DND1 in normal physiology and disease, however, is still virtually unknown and it therefore warrants further research.
authors.affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB, Groningen, The Netherlands. r.h.sijmons@medgen.umcg.nl
authors.forename: Rolf H
authors.initials: RH
authors.lastname: Sijmons
authors.forename: Yvonne J
authors.initials: YJ
authors.lastname: Vos
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Herkert
authors.forename: Krista K
authors.initials: KK
authors.lastname: Bos
authors.forename: Martijn F
authors.initials: MF
authors.lastname: Lutke Holzik
authors.forename: Josette E H M
authors.initials: JE
authors.lastname: Hoekstra-Weebers
authors.forename: Robert M W
authors.initials: RM
authors.lastname: Hofstra
authors.forename: Harald J
authors.initials: HJ
authors.lastname: Hoekstra
mesh_terms: D000328:Adult; D001483:Base Sequence; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D010375:Pedigree; D013736:Testicular Neoplasms / Q000235:genetics*
chemical_list: C528453:Dnd1 protein, human; D009363:Neoplasm Proteins
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