FOXL2 C402G mutation detection using MALDI-TOF-MS in DNA extracted from Israeli granulosa cell tumors

Objective: To develop a rapid, sensitive and reliable method to detect FOXL2 C402G mutation in granulosa cell tumor (GCT) and to investigate the prevalence of FOXL2 mutation in granulose cell tumors among Israeli patients. Methods: We designed and optimized a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) genotyping assay to detect FOXL2 C402G mutation in DNA isolated from formalin-fixed paraffin-embedded tissue samples. We examined 20 tumor samples obtained from Israeli patients diagnosed with granulose cell tumor. Results: Eighteen out of 20 samples were found to harbor FOXL2 C402G mutation. Pathological review of the two tumors harboring wild type FOXL2 (C402) concluded that they were adenocarcinomas and has been misclassified at initial diagnosis. We found that the prevalence of FOXL2 mutations among Israeli patients with GCT (100%) is similar to previous reports. Conclusions: Our results indicate that the FOXL2 mutations can be reliably detected by MALDI-TOF-MS genotyping. MALDI-TOF-MS genotyping is a simple, robust and highly sensitive method to detect FOXL2 C402G mutation. Our results confirm previous studies reporting over 95% prevalence of FOXL2 mutation in GCT. Furthermore, we suggest that testing for the presence of the FOXL2 C402G mutation may improve diagnostic accuracy.