Gonadal Development and Tumor Formation at the Crossroads of Male and Female Sex Determination

• Published in: Sexual development Vol. 5; no. 4; pp. 167 - 180
• Main Authors: Cools, M., Wolffenbuttel, K.P., Drop, S.L.S., Oosterhuis, J.W., Looijenga, L.H.J.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland 01.01.2011
• Subjects: Adolescent; Adult; Animals; Child; Child, Preschool; Chromosomes, Human, Y - genetics; Disorders of Sex Development - complications; Disorders of Sex Development - genetics; Female; Forkhead Box Protein L2; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - physiology; Humans; Infant; Infant, Newborn; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal - complications; Neoplasms, Germ Cell and Embryonal - genetics; Ovary - embryology; Review Article; Risk Factors; Sex Determination Processes - genetics; Sex Differentiation - genetics; SOX9 Transcription Factor - genetics; SOX9 Transcription Factor - physiology; SOXB1 Transcription Factors; Testis - embryology; Dysgerminoma; Germ cell tumor; Gonadoblastoma; Disorder of sex development; Carcinoma in situ; Gonadal development
• ISSN: 1661-5425; 1661-5433
• DOI: 10.1159/000329477

Malignant germ cell tumor (GCT) formation is a well-known complication in the management of patients with a disorder of sex development (DSD). DSDs are defined as congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. DSD patients in whom the karyotype – at least at the gonadal level – contains (a part of) the Y chromosome are at increased risk for neoplastic transformation of germ cells, leading to the development of the so-called ‘type II germ cell tumors’. However, tumor risk in the various forms of DSD varies considerably between the different diagnostic groups. This contribution integrates our actual knowledge on the pathophysiology of tumor development in DSDs, recent findings on gonadal (mal)development in DSD patients, and possible correlations between the patient’s phenotype and his/her risk for germ cell tumor development.