Molecular pathogenesis in granulosa cell tumor is not only due to somatic FOXL2 mutation

• Published in: Journal of ovarian research 2014-09, Vol.7 (1), p.88-88, Article 88
• Main Authors: Wang, Wen-Chung, Lai, Yen-Chein
• Format: Article
• Language: English
• Subjects: Aged, 80 and over; Analysis; Biopsy; Cancer; Care and treatment; Case Report; Case studies; Comparative Genomic Hybridization; Deoxyribonucleic acid; DNA; DNA Mutational Analysis; Experiments; Female; Forkhead Box Protein L2; Forkhead Transcription Factors - genetics; Genes; Genetic aspects; Genetic engineering; Genomes; Genotype; Granulosa Cell Tumor - diagnosis; Granulosa Cell Tumor - genetics; Humans; Hybridization; Immunohistochemistry; Loss of Heterozygosity; Mutation; Obstetrics; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - genetics; Pathogenesis; Studies; Tumorigenesis; Tumors
• ISSN: 1757-2215; 1757-2215
• DOI: 10.1186/s13048-014-0088-0

Granulosa cell tumors are rare ovarian malignancies. Their characteristics include unpredictable late recurrent and malignant behavior. Recent molecular studies have characterized the FOXL2 402C > G mutation in adult-type granulosa cell tumor. In this study, we report an 80-year-old woman with a granulosa cell tumor arising from ovary. She presented with a huge pelvic mass with postmenopausal bleeding. No obvious intraperitoneal tumor implants were observed during operation. Final diagnosis was granulosa-theca cell tumor without capsule invasion. No recurrent disease was noted during 3-year post-operation follow-up period. Molecular studies showed a heterozygous FOXL2 402C > G mutation in the tumor by direct gene sequencing. In addition, DNA replication error, on analysis of the lengths of CAG repeats in androgen receptor gene, revealed defective DNA mismatch repair system in the granulosa cell tumor. We propose that the 402C > G mutation in FOXL2 is critical to the development of adult granulosa cell tumor. However, the malignant behavior of this tumor is driven by DNA mismatch repair deficiency. Unequal DNA copy numbers were noted on array comparative genomic hybridization. This implies that there is malignant potential even in the early stage of the granulosa cell tumor. Late malignant recurrence may be a late event of DNA repair function disability, not directly related to pathognomonic FOXL2 mutation.