Which genetic mutations are commonly observed in ovarian cancers?

• A. BRCA1/BRCA2
• B. MLH1 or MSH2
• C. TP53
• D. All of the Above

Answer: (D)

Mutations in several genes that govern DNA repair and cell-cycle control are commonly seen in ovarian cancers. BRCA1 and BRCA2 mutations disrupt homologous recombination, a high-fidelity DNA repair pathway, which not only raises cancer risk but also makes tumors more susceptible to PARP inhibitors. TP53 mutations are especially pervasive in high-grade serous ovarian carcinoma, reflecting loss of the p53 tumor suppressor and leading to widespread genomic instability. MLH1 and MSH2 are mismatch repair genes; defects here cause microsatellite instability and are associated with Lynch syndrome, and they can appear in ovarian tumors as well, particularly in certain histologies or familial contexts. Because ovarian cancers arise across subtypes that can involve different DNA repair defects, all of these genetic alterations are observed, making “all of the above” the best answer.