title: The biology of germ cell tumors in disorders of sex development.
abstract: Development of a malignant germ cell tumor, i.e., germ cell cancer (GCC) in individuals with disorders of sex development (DSD) depends on a number of (epi-)genetic factors related to early gonadal- and germ cell development, possibly related to genetic susceptibility. Fetal development of germ cells is orchestrated by strict processes involving specification, migration and the development of a proper gonadal niche. In this review we will discuss the early (epi-)genetic events in normal and aberrant germ cell and gonadal development. Focus will be on the formation of the precursor lesions of GCC in individuals who have DSD. In our view, expression of the different embryonic markers in, and epigenetic profile of the precursor lesions reflects the developmental stage in which these cells are blocked in their maturation. Therefore, these are not a primary pathogenetic driving force. Progression later in life towards a full blown cancer likely depends on additional factors such as a changed endocrine environment in a susceptible individual. Genetic susceptibility is, as evidenced by the presence of specific risk genetic variants (SNPs) in patients with a testicular GCC, related to genes involved in early germ cell and gonadal development.
authors.affiliation: Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Remko
authors.initials: R
authors.lastname: Hersmus
authors.affiliation: Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Yolande
authors.initials: Y
authors.lastname: van Bever
authors.affiliation: Department of Pediatric Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Katja P
authors.initials: KP
authors.lastname: Wolffenbuttel
authors.affiliation: Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Katharina
authors.initials: K
authors.lastname: Biermann
authors.affiliation: Department of Pediatric Endocrinology, Ghent University Hospital and Ghent University, Ghent, Belgium.
authors.forename: Martine
authors.initials: M
authors.lastname: Cools
authors.affiliation: Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Leendert H J
authors.initials: LH
authors.lastname: Looijenga
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D012734:Disorders of Sex Development / Q000235:genetics* / Q000473:pathology; D004703:Endocrine System / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005854:Germ Cells / Q000378:metabolism; D006066:Gonads / Q000254:growth & development / Q000473:pathology; D006801:Humans; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor
keywords: disorders of sex development; germ cell cancer; germ cell neoplasia in situ; germ cell tumor; gonadal development; gonadoblastoma