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

Leendert H J Looijenga, Chia-Sui Kao, Muhammad T Idrees

Research output: Contribution to journalReview articlepeer-review

24 Citations (Scopus)


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.

Original languageEnglish
Article number5017
JournalInternational journal of molecular sciences
Issue number20
Publication statusPublished - 10 Oct 2019
Externally publishedYes


  • Animals
  • Biomarkers, Tumor
  • Biopsy
  • Cell Cycle Proteins
  • Chromosomes, Human, Y
  • Developmental Biology/methods
  • Disorders of Sex Development/diagnosis
  • Genetic Predisposition to Disease
  • Germ Cells
  • Gonadoblastoma
  • Gonads/pathology
  • Humans
  • Male
  • Nanog Homeobox Protein
  • Neoplasms, Germ Cell and Embryonal/diagnosis
  • Octamer Transcription Factor-3
  • Proto-Oncogene Proteins c-kit
  • Risk Factors
  • SOXF Transcription Factors
  • Testicular Neoplasms/diagnosis
  • Testis/pathology


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