Absence of the previously reported G protein oncogene (gip2) in ovarian granulosa cell tumors

The molecular pathogenesis of granulosa cell tumors of the ovary is not understood, although recent studies have shown that authentic inhibin secretion by these tumors may be used as a tumor marker. G proteins are heterotrimeric membrane-based polypeptides that mediate signal transduction. Activating mutations of the α-subunit have been reported in several tumors in which the resulting constitutively activated signal transduction pathway may be involved in tumorigenesis. Activating mutations of the G protein, Gα(i-2), have been reported to be present in 30% of ovarian sex cord tumors and in adrenocortical tumors; this activated Gα(i-2) has been designated the gip2 oncogene. We sought to explore the frequency of this oncogene in granulosa cell tumors, the most common of the sex cord tumors. Genomic DNA was obtained from either fresh-frozen tumor tissue or paraffin-embedded sections. Using both allele-specific oligonucleotide hybridization and direct sequencing of a PCR-amplified region of the Gα(i-2) gene, we were unable to confirm the presence of the previously reported mutation in any of the 13 tumors examined. The gip2 oncogene does not appear to be present at high frequency in ovarian granulosa cell tumors.