Utility of OCT3/4, TSPY and ß-catenin as biological markers for gonadoblastoma formation and malignant germ cell tumor development in dysgenetic gonads.

BACKGROUND: Gonadoblastoma (GB) is regarded as an in situ form of germ cell tumor in dysgenetic gonads, and 30% of patients with GB develop a dysgerminoma/seminoma tumor. OBJECTIVE: Determine whether OCT3/4 and ß-catenin are expressed in dysgenetic gonads before GB development and whether TSPY participates in the OCT3/4-ß-catenin pathways in the malignant invasive behavior. METHODS: dysgenetic gonads of Disorders of sex differentiation (DSD) patients with mixed gonadal dysgenesis were analyzed by immunohistochemistry and immunofluorescence for comparison with GB and dysgerminoma/seminoma. RESULTS: Our results suggest that the development of GB is secondary to the interaction of OCT3/4 and TSPY, that ß-catenin does not participate in this process. CONCLUSIONS: The use of this biological markers detects the potential high risk gonads.

Loss of cytochrome P450 17A1 protein expression in a 17alpha-hydroxylase/17,20-lyase-deficient 46,XY female caused by two novel mutations in the CYP17A1 gene.

17alpha-Hydroxylase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia caused by mutations in the CYP17A1 gene. This condition shows considerable clinical and biochemical variation. Molecular characterization of novel mutations in the CYP17A1 gene and detailed study of their structural, enzymatic, and clinical consequences are required to fully understand enzyme behavior. Here, we present the first molecular characterization of two novel mutations in CYP17A1 in a 15-year-old female Mexican mestizo 46,XY female with primary amenorrhea and lack of pubertal development and severe hypertension that manifested only after surgery. A complete clinical and biochemical evaluation was compatible with 17OHD. Structural anomalies in the CYP17A1 gene were discovered by direct automated sequencing, which revealed a novel compound heterozygous K110X/R362H mutation that leads to a complete lack of enzyme activity. Immunohistochemical analyses performed to determine protein expression and localization showed that cytochrome P450 17A1 was completely absent in the patient's testicular tissue. Studies of novel mutations, such as those described here, provide important information that allows us to better understand the effect of a given mutation on enzyme function and to observe the impact of the mutation on clinical phenotype.