CRISPR targeting of FOXL2 c.402C>G mutation reduces malignant phenotype in granulosa tumor cells and identifies anti-tumoral compounds.

Interestingly, the average fold induction of cell death relative to untreated cells was higher in CRISPR than in PARENTAL clones for both the highest dose treatments of dasatinib (5.3 vs 2.6) and ketoconazole (11.7 vs 4.4), with P values approaching significance ( P = 0.06 and P = 0.08, respectively). 3.4 Elimination of FOXL2 c. 402C>G mutation modifies the transcriptomic expression signature of granulosa tumor cells It has been previously described that mutation 402C>G in FOXL2 transcription factor, due to its location in the DNA‐binding domain, affects the expression of several target genes [ 26 ], changing the transcriptomic profile of granulosa cells.

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Interestingly, in a close to significance way, the percentage of senescent cells was increased among CRISPR clones when compared with the PARENTAL ones (Fig. 2c ).

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