Context: Conflicting data have been reported regarding the presence of a constitutive activation of Gs in ovarian granulosa cell tumors (OGCT). Although the precise role of this mutation in the transformation of ovarian cells into malignant cells remains debatable, it has been demonstrated in other tissues that the rate of cell proliferation and invasiveness can be influenced by the gsp oncogene.

Objective: To determine whether activating mutations of Gs or Gi are present in juvenile OGCTs and, if so, whether these mutations are significant prognostic factors.

Design and setting: Multicentric nationwide study.

Patients and methods: Thirty children with juvenile OGCT were included from the malignant germinal tumor protocol of the French Society for Childhood Cancer. Genetic studies of the tumoral DNA used nested PCR, laser microdissection and direct sequencing.

Results: Gs activating mutations in hot spot position 201 were found in 9 patients (30%). Laser microdissection confirmed that mutations R201C and R201H were exclusively localized in the tumoral granulosa cells and were absent in the ovarian stroma. Patients with a hyperactivated Gs exhibited a significantly more advanced tumor (P < 0.05) since 7 of them (77.7%) were staged as Ic or had had a recurrence. Gi did not exhibit any mutation.

Conclusions: 1. Activating mutations of Gs are present in 30% of juvenile ovarian granulosa cell tumors. 2. The gsp oncogene, which is known to be implicated in cell proliferation and tumoral invasiveness, can be considered as a new prognostic factor of these tumors.