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 no t understood, although recent studies have shown that authentic inhibi n secretion by these tumors may be used as a tumor marker. G proteins are heterotrimeric membrane-based polypeptides that mediate signal tra nsduction. Activating mutations of the alpha-subunit have been reporte d in several tumors in which the resulting constitutively activated si gnal transduction pathway may be involved in tumorigenesis. Activating mutations of the G protein, G alpha(i-2), have been reported to be pr esent in 30% of ovarian sex cord tumors and in adrenocortical tumors; this activated G alpha(i-2) has been designated the gip2 oncogene. We sought to explore the frequency of this oncogene in granulosa cell tum ors, the most common of the sex cord tumors. Genomic DNA was obtained from either fresh-frozen tumor tissue or paraffin-embedded sections. U sing both allele-specific oligonucleotide hybridization and direct seq uencing of a PCR-amplified region of the G alpha(i-2) gene, we were un able to confirm the presence of the previously reported mutation in an y of the 13 tumors examined. The gip2 oncogene does not appear to be p resent at high frequency in ovarian granulosa cell tumors.