Rare DICER1 and Absent FOXL2 Mutations Characterize Ovarian Juvenile Granulosa Cell Tumors

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• FOXL2 mutations are common in adult granulosa cell tumors, while DICER1 mutations are found in Sertoli-Leydig cell tumors.
• The presence and frequency of these mutations in juvenile granulosa cell tumors (JGCTs) remain controversial.
• Limited studies have investigated these specific genetic alterations in JGCTs.

Purpose of the Study:

• To determine the frequency of FOXL2 and DICER1 mutations in a large cohort of JGCTs.
• To assess the prognostic significance of these mutations in JGCTs.
• Clarify the genetic landscape of JGCTs.

Main Methods:

• Analysis of 50 juvenile granulosa cell tumors (JGCTs) for FOXL2 and DICER1 mutations.
• Review and reclassification of cases with identified mutations.
• Statistical analysis to evaluate prognostic impact.

Main Results:

• FOXL2 hotspot mutations were absent in the 50 JGCTs; 2 cases were reclassified as adult granulosa cell tumors.
• DICER1 mutations were identified in 3 out of 47 pathologically confirmed JGCTs (6%).
• One case with a DICER1 mutation was reclassified as gynandroblastoma with a JGCT component.

Conclusions:

• FOXL2 mutations are not associated with juvenile granulosa cell tumors.
• DICER1 mutations occur in a small subset of JGCTs, suggesting a role in a specific subtype.
• These findings refine the understanding of genetic drivers in ovarian tumors.