Activating mutations of the stimulatory g protein in juvenile ovarian granulosa cell tumors: a new prognostic factor?

The Journal of Clinical Endocrinology and Metabolism
N KalfaC Sultan

Abstract

Conflicting data have been reported regarding the presence of a constitutive activation of Galphas 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. The objective of this study was to determine whether activating mutations of Galphas or Galphai are present in juvenile OGCTs and, if so, whether these mutations are significant prognostic factors. This was a multicentric nationwide study. 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. Galphas-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 Galphas exhibited a significantly more advanced tumor (P < 0.05) because seven of them (77.7%) w...Continue Reading

Citations

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