Next Article in Journal
B-Cell Activating Factor Enhances Hepatocyte-Driven Angiogenesis via B-Cell CLL/Lymphoma 10/Nuclear Factor-KappaB Signaling during Liver Regeneration
Previous Article in Journal
Caenorhabditis Elegans and Probiotics Interactions from a Prolongevity Perspective
Previous Article in Special Issue
46,XX DSD due to Androgen Excess in Monogenic Disorders of Steroidogenesis: Genetic, Biochemical, and Clinical Features
Open AccessReview

Predicting Gonadal Germ Cell Cancer in People with Disorders of Sex Development; Insights from Developmental Biology

1
Professor Translational Patho-Oncology, Department of Pathology, Lab. for Experimental Patho-Oncology, Erasmus MC-University Medical Center Rotterdam, and Group Looijenga, Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands
2
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
3
Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
*
Author to whom correspondence should be addressed.
Shared last authorship.
Int. J. Mol. Sci. 2019, 20(20), 5017; https://doi.org/10.3390/ijms20205017
Received: 19 August 2019 / Revised: 3 October 2019 / Accepted: 5 October 2019 / Published: 10 October 2019
(This article belongs to the Special Issue Molecular Aspects of Sex Development in Mammals: New Insight)
The risk of gonadal germ cell cancer (GGCC) is increased in selective subgroups, amongst others, defined patients with disorders of sex development (DSD). The increased risk is due to the presence of part of the Y chromosome, i.e., GonadoBlastoma on Y chromosome GBY region, as well as anatomical localization and degree of testicularization and maturation of the gonad. The latter specifically relates to the germ cells present being at risk when blocked in an embryonic stage of development. GGCC originates from either germ cell neoplasia in situ (testicular environment) or gonadoblastoma (ovarian-like environment). These precursors are characterized by presence of the markers OCT3/4 (POU5F1), SOX17, NANOG, as well as TSPY, and cKIT and its ligand KITLG. One of the aims is to stratify individuals with an increased risk based on other parameters than histological investigation of a gonadal biopsy. These might include evaluation of defined susceptibility alleles, as identified by Genome Wide Association Studies, and detailed evaluation of the molecular mechanism underlying the DSD in the individual patient, combined with DNA, mRNA, and microRNA profiling of liquid biopsies. This review will discuss the current opportunities as well as limitations of available knowledge in the context of predicting the risk of GGCC in individual patients. View Full-Text
Keywords: germ cell cancer; developmental pathogenesis; individual risk assessment; prediction; disorders of sex development germ cell cancer; developmental pathogenesis; individual risk assessment; prediction; disorders of sex development
Show Figures

Figure 1

MDPI and ACS Style

Looijenga, L.H.J.; Kao, C.-S.; Idrees, M.T. Predicting Gonadal Germ Cell Cancer in People with Disorders of Sex Development; Insights from Developmental Biology. Int. J. Mol. Sci. 2019, 20, 5017.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop