NO EVIDENCE OF A ROLE FOR MUTATIONS OR POLYMORPHISMS OF THE FOLLICLE-STIMULATING-HORMONE RECEPTOR 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 immunoreactive i nhibin secretion by these tumors may be used as a tumor marker. Granul osa cell tumors exhibit many features of normal granulosa cells, inclu ding a response to FSH and inhibin secretion. FSH levels are suppresse d in patients with inhibin-secreting granulosa cell tumors, suggesting FSH-independent growth of these tumors. Activating mutations of the F SH receptor might, therefore, be involved in tumorigenesis. We sought to identify mutations in the FSH receptor genes of these tumors using PCR to amplify the exon encoding the transmembrane and cytoplasmic dom ains from the tumor DNA. Analysis of the amplicons for single strand c onformational polymorphisms and direct sequencing confirmed a previous ly reported polymorphism in the C-terminal region of the receptor, but did not identify tumor-specific missense mutations and/or polymorphis ms. In addition, ribonucleic acid from 3 granulosa cell tumors was use d to confirm expression of the FSH receptor; expression was unexpected ly also observed in several ovarian mucinous cystadenocarcinomas used as controls. In conclusion, our failure to identify activating mutatio ns of the FSH receptor in 15 granulosa cell tumors argues against a ro le for the FSH receptor in tumorigenesis and suggests that some subseq uent component of this signal transduction pathway may be activated.