Pathogenesis of Granulosa-Cell Tumors of the Ovaries

The histopathologic diagnosis of granulosa-cell tumors (GCTs) — neoplasms that constitute <5% of ovarian cancers — is difficult even with immunohistochemical stains. To identify potential genetic mutations associated with GCT pathogenesis, investigators studied tissue from four adult-type GCTs using whole-transcriptome, paired-end RNA sequencing. For primary validation, they also analyzed samples from additional adult-type GCTs as well as juvenile-type GCTs, other ovarian tumors, and breast carcinomas.

All four adult-type GCTs contained the 402C→G point mutation in the FOXL2 gene (which encodes a transcription factor critical for GCT development). Of note, this point mutation also was present in some juvenile-type GCTs and thecomas but was a…