〔Abstract〕 Objective To find molecular targets related to the occurrence and development of ovarian cancer induced by whole-exome sequencing and to verify the mechanismin vitrocell experiments. Methods 8 pairs of serous ovarian cancer tissues were sequenced using whole-exome, and another 43 serous ovarian cancer tissues and 156 peripheral blood samples of normal women were performed target gene sequencing. In thein vitroexperiment, the plasmids containing theCREBBPgene L1850 fs and P1373 S mutations were transfected into human serous ovarian cancer cell line A2780 with Lipofectamine 3000, and the plasmids containing wild-typeCREBBPand the empty vector were used as controls. CRP protein expression afterCREBBPL1850 fs and P1373 S mutated was evaluated by Western blot; cell proliferation of L1850 fs and P1373 S mutation was detected by CCK-8 assay; cell migration of L1850 fs and P1373 S mutation was detected by Transwell chamber test; cells invasion of L1850 fs and P1373 S mutation was detected by scratch test. Results Two high-frequency mutation sites ofCREBBPgene on L1850 fs(c.5548 dupC) and P1373 S(c.4117 C>T) in serous ovarian cancer tissues were discovered using whole exome sequencing. L1850 f was a frameshift mutation, and P1373 S was a non-synonymous sequence. In 51 cases of serous ovarian cancer(8 cases of whole exome sequencing, 43 cases of target gene sequencing), the mutation rate ofCREBBPgene was 41.2%, while the mutation rate of normal female peripheral blood was 21.8%, the difference was statistically significant(χ2=7.4,P=0.007). The results of western blotting showed that the L1850 fs mutation could reduce the expression of CBP in ovarian cancer cell, while the P1373 S mutation had no significant effect on CBP protein expression. CCK-8 analysis showed that mutantCREBBPcould promote the proliferation of ovarian cancer cells. Transwell chamber test showed that L1850 fs and P1373 S mutation could promote the migration of ovarian cancer cells. Scratch test analysis showed that L1850 fs and P1373 S mutation could increase the invasion ability of ovarian cancer cells. Conclusion In this experiment, two point mutations ofCREBBPin L1850 fs and P1373 S were found in serous ovarian cancer using whole exome sequencing. Further cell experiments showed that the two mutation could promote the proliferation, invasion and metastasis of ovarian cancer cells by affecting the CBP protein, suggesting thatCREBBPL1850 fs and P1373 S might become new targets for the diagnosis and treatment of ovarian cancer.