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SRY mutation and tumor formation on the gonads of XP pure gonadal dysgenesis patients
S Uehara1, T Funato, N Yaegashi
1Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan.
Abstract:
We report three patients with XY pure gonadal dysgenesis. Two of these patients developed gonadoblastoma and associated dysgerminoma. Molecular analyses were undertaken to investigate the relationship between the formation of these tumors and Y chromosome aberrations. Deletion analyses were performed by polymerase chain reaction (PCR) amplification of Y chromosome-specific DNA sequences (PABY, SRY, DYS250, DYS254, and DYZ1). A cryptic deletion of the short arm of the Y chromosome that included the PABY, SRY, DYS250, and DYS254 loci was observed in one of the patients (22-years-old) with an associated tumor. In the other two patients who did not demonstrate such a deletion, the sequence of the SRY open reading frame was determined by the dideoxynucleotide method. Two nucleotide substitutions followed by a seven nucleotide deletion were observed in the 3' end of HMG (high mobility group)-box in the other patient (15-years-old) with an associated tumor. The patient (22-years-old) without an associated tumor did not have the cryptic deletion or mutation of SRY. A Y chromosome specific sequence (DYZ1) was demonstrated by PCR amplification of microdissected tumor tissues from these two patients. These results suggest that SRY may play a role in the formation of gonadal tumors, especially dysgerminoma.
Insights
Y chromosome aberrations, specifically SRY gene mutations, are linked to gonadal tumor development in patients with XY pure gonadal dysgenesis. These findings highlight SRY
Area of Science:
- Genetics
- Oncology
- Endocrinology
Background:
- Pure gonadal dysgenesis (PGD) is a disorder of sex development where individuals with a Y chromosome develop streak gonads.
- Patients with XY PGD have an increased risk of developing gonadal tumors, including gonadoblastoma and dysgerminoma.
Observation:
- Three patients with XY PGD were studied for Y chromosome aberrations.
- Two patients developed gonadoblastoma and dysgerminoma.
- Molecular analyses, including PCR and dideoxynucleotide sequencing, were performed on patient DNA and tumor tissues.
Findings:
- A cryptic deletion in the Y chromosome's short arm, encompassing PABY, SRY, DYS250, and DYS254 loci, was found in a tumor-bearing patient.
- A mutation in the SRY gene's HMG-box was identified in another tumor-bearing patient.
- Y chromosome-specific sequences (DYZ1) were detected in tumor tissues from both patients with tumors.
Implications:
- The SRY gene, crucial for male sex determination, may also play a role in gonadal tumor formation in XY PGD.
- These findings suggest SRY aberrations are implicated in the pathogenesis of gonadoblastoma and dysgerminoma.
- Further research into SRY's function in gonadal development and tumorigenesis is warranted.