Whole Genome Analysis of Ovarian Granulosa Cell Tumors Reveals Tumor Heterogeneity and a High-Grade TP53-Specific Subgroup.
作者： Joline Roze , Glen Monroe , Joachim Kutzera , Jolijn Groeneweg , Ellen Stelloo
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摘要: Adult granulosa cell tumors (AGCTs) harbor a somatic FOXL2 c.402C>G mutation in ~95% of cases and are mainly surgically removed due to limited systemic treatment effect. In this study, potentially targetable genomic alterations AGCTs were investigated by whole genome sequencing on 46 tumor samples matched normal DNA. Copy number variant (CNV) analysis confirmed gain chromosome 12 14, loss 22. Pathogenic TP53 mutations identified three patients with highest mutational burden mitotic activity, defining high-grade AGCT subgroup. Within-patient comparisons showed 29-80% unique per sample, suggesting heterogeneity. A higher was found recurrent tumors, as compared primary AGCTs. FOXL2-wildtype harbored DICER1, TERT(C228T) similar CNV profiles FOXL2-mutant tumors. Our study confirms that absence the does not exclude diagnosis. The lack overlapping variants cancer genes indicates need for personalized patients.
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