TY - JOUR
T1 - Predicting Gonadal Germ Cell Cancer in People with Disorders of Sex Development; Insights from Developmental Biology
AU - Looijenga, Leendert H J
AU - Kao, Chia-Sui
AU - Idrees, Muhammad T
N1 - Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/10/10
Y1 - 2019/10/10
N2 - 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.
AB - 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.
KW - Animals
KW - Biomarkers, Tumor
KW - Biopsy
KW - Cell Cycle Proteins
KW - Chromosomes, Human, Y
KW - Developmental Biology/methods
KW - Disorders of Sex Development/diagnosis
KW - Genetic Predisposition to Disease
KW - Germ Cells
KW - Gonadoblastoma
KW - Gonads/pathology
KW - Humans
KW - Male
KW - Nanog Homeobox Protein
KW - Neoplasms, Germ Cell and Embryonal/diagnosis
KW - Octamer Transcription Factor-3
KW - Proto-Oncogene Proteins c-kit
KW - Risk Factors
KW - SOXF Transcription Factors
KW - Testicular Neoplasms/diagnosis
KW - Testis/pathology
UR - http://www.scopus.com/inward/record.url?scp=85074234245&partnerID=8YFLogxK
U2 - 10.3390/ijms20205017
DO - 10.3390/ijms20205017
M3 - Review article
C2 - 31658757
SN - 1422-0067
VL - 20
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 20
M1 - 5017
ER -