This Article Full Text Full Text (PDF) All Versions of this Article: 91/5/1842    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kalfa, N. Articles by Sultan, C. Search for Related Content PubMed PubMed Citation Articles by Kalfa, N. Articles by Sultan, C. Related Collections Endocrine Oncology Female Endocrinology

Activating Mutations of the Stimulatory G Protein in Juvenile Ovarian Granulosa Cell Tumors: A New Prognostic Factor?

Unité d’Endocrinologie-Gynécologie Pédiatrique (N.K., A.E., F.A., S.L., C.S., F.P.), Service de Pédiatrie 1, Hôpital Arnaud-de-Villeneuve, and Service d’Hormonologie du Développement et de la Reproduction, Hôpital Lapeyronie, Centre Hospitalier Universitaire (CHU) Montpellier, 34295 Montpellier, France; Institut National de la Santé et de la Recherche Médicale U540 (N.K., S.L., C.S.), Hormones et Cancers, 34000 Montpellier, France; Service d’Oncologie Pédiatrique (C.Pa.), Institut Gustave Roussy, 94805 Villejuif, France; Service d’Anatomo-pathologie (P.D.), Institut Gustave Roussy, 94805 Villejuif, France; Service d’Endocrinologie Pédiatrique (C.Pi.), Hôpital des Enfants, CHU Toulouse, 31059 Toulouse, France; Service d’Endocrinologie Pédiatrique (E.T.), Hôpital Necker, Assistance Publique–Hôpitaux de Paris (APHP), 75743 Paris, France; Service d’Endocrinologie Pédiatrique (R.B.), Hôpital Kremlin-Bicêtre, APHP, 94270 Paris, France; Service d’Endocrinologie Pédiatrique (C.L.), Hôpital Charles Nicolle, CHU Rouen, 76031 Rouen, France; Service de Pédiatrie (D.P.), CHU Grenoble, 38043 Grenoble, France; Service d’Endocrinologie (A.-M.G.), Hôpital Caremeau, CHU Nîmes, 30029 Nîmes, France; and Service d’Anatomopathologie (P.B.), Hôpital Lapeyronie, CHU Montpellier, 34295 Montpellier, France

Address all correspondence and requests for reprints to: Prof. Charles Sultan, Unité d’Endocrinologie-Gynécologie Pédiatriques, Service de Pédiatrie 1, Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire Montpellier, 34295 Montpellier, France. E-mail: c-sultan{at}chu-montpellier.fr.

Context: Conflicting data have been reported regarding the presence of a constitutive activation of Gs in ovarian granulosa cell tumors (OGCTs). 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: The objective of this study was 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: This was a 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 nine 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) because seven of them (77.7%) were staged as Ic or had had a recurrence. Gi did not exhibit any mutation.

Conclusions: Activating mutations of Gs are present in 30% of juvenile OGCTs. 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.