. 2017 Sep 27;7(5):391–399. doi: 10.3892/br.2017.990

Table I.

Candidate genes enhancing synthetic lethality of PARP inhibitors in CCC.

A, Candidate mutated genes for enhancing the therapeutic ratio achieved by PARP inhibitors in CCC

Official symbol	Official full name	Function	Candidate synthetic lethality gene partners	Somatic mutations in CCC	Refs.
ARID1A	AT-rich interaction domain 1A	Chromatin remodeling	ATR		26,30,31,32
ATM^a	Ataxia telangiectasia mutated serine/threonine kinase	DNA repair checkpoint	PARP, TOP1, ATR	Somatic HR mutation in CCC, ATM c.5441delT	16,37,39
ATR^a	TM and Rad3-related	DNA repair checkpoint	PARP		10,29,37,38
BARD1^a	BRCA1-associated RING domain 1	HR	PARP	Expression of spliced isoforms of BARD1 was typical for clear cell carcinoma (51)	39,40
BRCA1/2^a	BRCA1, DNA repair associated	HR	PARP	Somatic HR mutation in CCC, BRCA1 1135insA, BRCA2 p.S368X	5,16
CDKN2A	Cyclin dependent kinase inhibitor 2A	Cell cycle regulator	RB1		45
CHEK1^a	Checkpoint kinase 1	DNA repair checkpoint	ATR, MYC, TP53, Wee1, p21	CHK1 is a homologous recombination gene	10,29
CHEK2	Checkpoint kinase 2	DNA repair checkpoint		CHEK2 p.S428F and CHEK2 del exon 1–7	9,16
CREBBP	CREB binding protein		p300		58
ERBB2	erb-b2 receptor tyrosine kinase 2, HER2	Oncogene	PARP		26,46
FANCD2	Fanconi anemia complementation group D2	DNA repair	PARP, POLQ		67
KRAS	KRAS proto-oncogene, GTPase	Oncogene	XIAP, RAD51		43
LZTS1	Leucine zipper tumor suppressor 1	Tumor suppressor	CDKN2A/2B		45
MLH1	mutL homolog 1	DNA mismatch repair	ATR		27,33,39
MRE11A^a	MRE11 homolog, double strand break repair nuclease	DNA repair	PARP	Somatic HR mutation in CCC, MRE11A c.1196insTT	41
MSH6	mutS homolog 6	DNA mismatch repair	DHFR, POLB, POLG, PINK1
MTOR	Mechanistic target of rapamycin kinase	Cell cycle regulator	TP53		42,44
NF1	Neurofibromin 1	Oncogene	PARP		44
NOTCH1	Notch 1	Cell processes	ERBB2, EGFR		68
PIK3CA	Phosphatidylinositol-4,5 bisphosphate3-kinase catalytic subunit alpha	Oncogene	TRRAP, Hh		27,29
PPP2R1A	Protein phosphatase 2 scaffold subunit Aalpha	Cell growth	PLK	7% of CCC had mutations in PPP2R1A.	30
PRKDC	Protein kinase, DNA-activated, catalytic polypeptide	DNA repair	MYC, MSH3		24
PTEN	Polypeptide phosphatase and tensin homolog	Tumor suppressor	PARP, ATM, NLK	10% of CCC had mutations in PTEN. Somatic HR mutation in CCC, PTEN c.678delC, PTEN c.968insA, PTEN p.R233X	16,28,33
RAD51C	RAD51 paralog C	DNA repair	PARP		14,43
PALB2	Partner and localizer of BRCA2	BRCA2 complex	PARP		69
TP53	Tumor protein p53	Cell cycle regulator	ID1, CHK1, ATM, ATR, mTOR		3,39,44
XRCC5	X-ray repair cross complementing 5	DNA repair	Ku		50

B, Upregulated genes enhancing synthetic lethality of PARP inhibitors in CCC

Official symbol	Official full name		Function	Candidate synthetic lethality gene partners	Refs.

AURKA	Aurora kinase A		Cell cycle regulator	MYC	5,51
CCNE1^a	Cyclin E1		Cell cycle regulator	PARP	47,54
CKS1B^a	CDC28 protein kinase regulatory subunit 1B		Cell cycle regulator	PLK1	48
ERBB2	erb-b2 receptor tyrosine kinase 2 (HER2)		Oncogene	NOTCH1 PARP	26,46
HNF1B	Hepatocyte nuclear factor-1β		Transcription factor	CHEK1	49
PTEN^a	Phosphatase and tensin homolog		Tumor suppressor	PARP, ATM, NLK, (nemo like kinase)	33,35,36
XRCC5	X-ray repair cross complementing 5		DNA repair	Ku	50

C, Synthetic lethal gene partners based on chemoresistance-related genes in CCC

Official symbol	Official full name		Function	Candidate synthetic lethality gene partners	Refs.

CHEK1^a	Checkpoint kinase 1		DNA repair checkpoint	ARR, MYC, TP53, Wee1, p21	29,60,61,62,63
DNMT1^a	DNA methyltransferase 1		Methyltransferase	PARP	56,64
FGFR2^a	Fibroblast growth factor receptor 2		Oncogene	PTEN	57
ERBB2^a	erb-b2 receptor tyrosine kinase 2		Oncogene	PARP	26
MYC^a	MYC proto-oncogene, bHLH transcription factor		Oncogene	PTEN	52,58
NOTCH1^a	Notch 1		Cell processes	EGFR	27,59,66

BRCA1/2, but also ATM, ATR, BARD1, CCNE1, CHEK1, CKS1B, DNMT1, ERBB2, FGFR2, MRE11A, MYC, NOTCH1 and PTEN were considered as candidate genes for synthetic lethality gene partners for PARP inhibitors.