Disorders of sex development patients with Y chromosome materials have a significantly increased risk of GCTs. Gonadoblastoma and dysgerminoma/seminoma are the most prevalent GCTs and 46, XY PGD carries the highest tumour presence and malignancy risk. AIS could postpone bilateral gonadectomy until or after adolescence, while others with streak gonads should undergo surgery as soon as diagnosis. Specific serum tumour markers could be used in predicting GCTs and monitoring. Optimal care and close follow-up are required.
The objective of this study was to examine risks for gonadal malignancy in a large sample of adult female patients with disorders of sex development (DSD). A retrospective-observational study was conducted from July 1992 to March 2015 and 202 women with DSD were enrolled. Tumor risks for different types of DSD were measured. We found that the patients' total gonadal-malignancy risk was 18.3% (37/202). Tumors included gonadoblastoma (n = 11), seminoma (n = 8), dysgerminoma (n = 5), choriocarcinoma (n = 1), sertoli cell tumors (n = 11), and leydig cell tumors (n = 1). The incidence of gonadal malignancy in patients with complete androgen insensitivity syndrome (CAIS), pure 46, XY gonadal dysgenesis, 45 X/46 XY mixed gonadal dysgenesis, 17α-hydroxylase/17, 20-lyase deficiency and partial androgen insensitivity syndrome (PAIS) were 27.1% (13/48), 22.4% (15/67), 10.9% (5/46), 10% (2/20) and 9.5% (2/21), respectively. Our results suggest that the incidence of gonadal malignancy increases with age for female patients with Y-chromosome material. Upon diagnoses, immediate, prophylactic gonadectomies should be considered for adult female patients with DSD containing Y chromosome material if they cannot receive regular follow-ups.
Tumorigenesis is frequently accompanied by enhanced rRNA transcription, but the signaling mechanisms responsible for such enhancement remain unclear. Here, we report evidence suggesting a novel link between deregulated Hedgehog signaling and the augmented rRNA transcription in cancer. Aberrant activation of the Hedgehog pathway in keratinocytes is a hallmark of basal cell carcinoma (BCC), the most common cancer in light-skinned individuals. We show that Gli proteins, downstream effectors of the Hedgehog pathway, increase expression of a novel rRNA gene (rDNA) transcription factor, basonuclin, whose expression is markedly elevated in BCCs. The promoter of the human basonuclin gene contains a Gli-binding site, which is required for Gli protein binding and transcriptional activation. We show also that the level of 47S pre-rRNA is much higher in BCCs than in normal epidermis, suggesting an accelerated rRNA transcription in the neoplastic cells. Within BCC, those cells expressing the highest level of basonuclin also exhibit the greatest increase in 47S pre-rRNA, consistent with a role for basonuclin in increasing rRNA transcription in these cells. Our data suggest that Hedgehog-Gli pathway enhances rRNA transcription in BCC by increasing basonuclin gene expression.
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