Adult granulosa cell tumours s by
incidence and risk of
ovarian cancer, with adult granulosa cell tumour at right Using next generation
DNA sequencing, 97% of adult granulosa cell tumours were found to contain an identical mutation in the
FOXL2 gene . This is a somatic mutation, meaning it is not usually transmitted to descendants. Mutation c.402C>G in the sequence of FOXL2 leads to the amino acid substitution p. C134W. It is believed that this mutation may be the cause of granulosa cell tumours.
Juvenile granulosa cell tumours Two recent studies show that the enzyme
AKT1 is involved in juvenile granulosa cell tumours. In-frame duplications in the pleckstrin-homology domain of the protein were found in more than 60% of juvenile granulosa cell tumours occurring in girls under 15 years of age. The tumours without duplications carried point mutations affecting highly conserved residues. The mutated proteins carrying the duplications displayed a non-wild-type subcellular distribution, with a marked enrichment at the plasma membrane, leading to a strong activation of AKT1. Analysis by RNA-Seq pinpointed a series of differentially expressed genes that are involved in cytokine and hormone signaling and cell division-related processes. Further analyses pointed to a possible dedifferentiation process, and suggested that most of the transcriptomic dysregulations might be mediated by a limited set of transcription factors perturbed by AKT1 activation. These results incriminate somatic mutations of AKT1 as probable driver events in the pathogenesis of juvenile granulosa cell tumours. ==Diagnosis==