Discovery of genetic biomarkers contributing to variation in drug response of cytidine analogues using human lymphoblastoid cell lines

Table 3 Functional studies of candidate genes

Gene symbol	Selection strategy			Cytotoxicity validation in cancer cell lines
	SNP vs. IC50		Integrated analysis	Both SU86 and MDA231	Either THP-1 or BDCM
	SNP Location	P < 10-4	SNP vs. Exp P < 10-4	(cancer cell lines)	(leukemia cell lines)
	SNP Location	P < 10-4	Exp vs. IC50 P <10-4	(cancer cell lines)	(leukemia cell lines)
*PIGB*	Intron/coding/5UTR/3UTR	Gem	Gem	Yes	NP
C3orf23	5UTR/upstream	Gem	Gem	No	NP
*ZADH2*			Gem	Yes	NP
ARHGEF12			Gem	No	NP
DPP7			Gem	No	NP
*PSME3*			Gem	Yes	NP
NIPSNAP3B	Intron/5UTR	Gem		No	NP
PIK3R1	Flanking_5UTR/3UTR	Gem		No	NP
*DOK6*	Intron	Gem		Yes	NP
*TGFBI*	Flanking_5UTR	Gem		Yes	NP
UNC13C			AraC	No	No
*C14orf169*			AraC	Yes	NP
MAP4K4			AraC	No	NP
URB2	Downstream	AraC		No	No
*TUSC3*	Intron/5UTR/3UTR	AraC		Yes	No
LARS2	5UTR	AraC		Yes	No
*RIS1 (TMEM158)*	5UTR	AraC		Yes	Yes
IGSF4 (CADM1)	Intron/downstream/3UTR	AraC		No	No
*LNX2*	Intron/5UTR/3UTR	AraC		Yes	No
*SMC2*	3UTR	AraC		Yes	Yes
PLD5	Intron	Both		No	NP
GPR98	Intron	Both		No	No
*HLA-DRA*	Intron/3UTR	Both		Yes	No
ZNF215	Flanking_5UTR/3UTR/coding	Both		No	No
CABLES1			Both	No	No

The table lists the top 26 candidate genes selected for siRNA screening for both gemcitabine and AraC, with MTS assay results as well as QRT-PCR assay results when appropriate.
A total of 26 genes were selected for siRNA screening, with 11 genes for gemcitabine, 10 for AraC, and 5 for both. For the validation assays with MTS and QRT-PCR, “Yes” indicates that knockdown of the gene altered drug cytotoxicity, while “No” indicates no alteration. “NP” indicates not performed. The genes that are bolded were functionally validated.

ISSN: 1471-2164