Table 3.

Overview of the most important DNA repair genes, their predisposition and prognostic impact and potential therapeutic use in targeted therapy for OvC. Symbols: ↑ means higher, or better; ↓ means lower, or worse. Protein names: breast cancer 1 and 2 (BRCA1 and 2), RAD51 paralog C and paralog D (RAD51C and D), RAD50 homolog 1 (RAD50), partner and localizer of BRCA2 (PALB2), BRCA1-interacting protein C-terminal helicase (BRIP1), PMS1 homolog 2 (PMS2), X-ray repair cross-complementing 4 (XRCC4), DNA ligase 4 (LIG4), MutS homolog 6 (MSH6), MutL homolog 1 (MLH1), PMS1 homolog 2 (PMS2), 8-oxoguanine DNA glycosylase 1 (OGG1), MutY DNA glycosylase (MUTYH), apurinic/apyrimidinic endonuclease 1 (APE1), X-ray repair cross-complementing 1 (XRCC1), poly(ADP-ribose) polymerase 1 (PARP1), xeroderma pigmentosum complementation protein C and D (XPC and D/ERCC2), excision repair cross-complementation group 1 (ERCC1), O⁶-methylguanine DNA methyltransferase (MGMT), alpha-ketoglutarate-dependent dioxygenase AlkB (ALKB).

DNA Repair Pathway	Gene	Predisposition Impact	Prognostic Impact	Therapeutic Potential (or Use)
Homologous recombination repair	BRCA1	Mutations associated with ↑ risk [45] and earlier onset [46]	↑ OS vs. non-carriers [50]	Better response to platinum-based chemotherapeutics [50,53], response to PARPi [55,229]
	BRCA2	Mutations associated with ↑ risk [45] and earlier onset [46]	↑ OS vs. non-carriers [50]	Better response to platinum-based chemotherapy [50,53], response to PARPi [55,229]
	RAD51C	Mutations associated with ↑ risk [59,60] and earlier onset [60]	N/A	Response to PARPi (in vivo and in vitro evidence) [64,65]
	RAD51D	Mutations associated with ↑ risk [9,61,62,63] and earlier onset [60]	N/A	Response to PARPi (in vivo and in vitro evidence) [65]
	RAD50	Mutated in about 0.12% of tumors [66]	Copy number deletion associated with ↑ OS and PFS [69]	In vitro knock-down associated with better response to PARPi [69]
	PALB2	Mutations associated with ↑ risk [73]	N/A	Response to PARPi (in vivo and in vitro evidence) [74,75]
	BRIP1	Mutations associated with ↑ risk [62,82,83,84]	N/A	Likely to predispose the response to PARPi and platinum [55]–needs further evaluation
Non-homologous end joining	XRCC4	N/A	↑ expression associated with ↓ OS [106]	N/A
	LIG4	Possible involvement of SNPs needs further evaluation	N/A	N/A
Mismatch repair	MSH6	N/A	N/A	Deficiency predisposes to platinum sensitivity in clear cell carcinoma [230]
	MLH1	Mutations associated with ↑ risk of Lynch syndrome-associated OvC [231]	↓ expression associated with ↑ OS and PFS [232]	N/A
	PMS2	Germline mutation associated with ↑ risk of Lynch syndrome-associated OvC [233]	N/A	N/A
Base excision repair	OGG1	SNPs associated with ↑ risk [90,91,132]	N/A	N/A
	MUTYH	Biallelic mutation associated with ↑ risk [135]	N/A	N/A
	APE1	SNP associated with ↑ risk [93]	↑ expression [139] and cytoplasmatic localization [140,141] have ↓ prognosis and OS	N/A
	XRCC1	SNP associated with ↑ risk [94]	SNPs [95,96,234,235] and ↑ expression [142] associated with ↓ prognosis	N/A
	PARP1	N/A	N/A	PARPi approved application for patients with germline BRCA1/2 mutations, with germline or somatic mutation BRCA1/2 with relapsed illness or with relapsed illness sensitive to platin-derivate chemotherapy regardless to BRCA status (FDA and EMA guidlines)
Nucleotide excision repair	XPC	N/A	SNPs associated with ↑ PFS [236]	N/A
	XPD/ERCC2	SNP associated with ↑ risk [237]	SNPs associated with prognosis [238]	SNP associated with severe neutropenia in patients treated by cisplatin-based chemotherapy [239]
	ERCC1	N/A	SNPs associated with ↑ OS [240]	SNP associated with ↑ risk of nephrotoxicity in patients treated by cisplatin-based chemotherapy [239]
Direct repair	MGMT	N/A	N/A	Likely to drive chemoresistance [170]
	ALKB	N/A	N/A	ALKBH5 downregulation contributes to PARPi resistance in BRCA-deficient EOC [241]