CCI-779 (Temsirolimus) exhibits increased anti-tumor activity in low EGFR expressing HNSCC cell lines and is effective in cells with acquired resistance to cisplatin or cetuximab

Table 2 Mutations identified by panel next-generation sequencing for cell lines (upper panel) and resistance models (lower panel) used in this study

Cell line	Cell cycle control	*TP53*	Cell death regulation	RTK signaling	PI3K-akt signaling	MAPK-signaling	Others
UT-SCC-23		DEL					*SMAD4,* FAT1
UM-SCC-11B		Cys110Ser
UD-SCC-5		His47Tyr		ERBB4, PDGFR			FAT1, PCDH15
UD-SCC-4		DEL		KDR, MYC			FAT1, PCDH15
UM-SCC-22B		Tyr88Cys	CASP8	KIT			*NOTCH1, SMAD4,* FAT1, PCDH15,
SCC-9		Val142fs		*KDR, RET*			FAT1, Notch1, PCDH15
UM-SCC-17B				EGFR, KDR, KIT	PIK3CA	HRAS	*SMAD4,* FAT1
UM-SCC-74B				KDR, KRAS			CDH1, FAT1, NOTCH1, PCDH15
UT-SCC-15	*CDKN2A*	Arg282Trp	CASP8				CDH1, FAT1
UM-SCC-25	*CDKN2A*			ERBB4			*SMAD4,* FAT1
FaDu _CDDP-S/R	CDKN2A	Arg248Leu 2% ➔ 47%					*SMAD4*
UD-SCC-4 _CDDP-S/R		DEL		MYC, *KDR 70% ➔ 100%*			FAT1, PCDH15, NSD1 0% ➔ 38%
UT-SCC-9 _CET-S/R	*CDKN2A*	DEL		MET 35% ➔ 50%			FAT1
UM-SCC-22B _CET-S/R		Tyr88Cys	CASP8	KIT			*NOTCH1, SMAD4,* FAT1, PCDH15

Mutations which affect protein function, as predicted by the SIFT [41] and PolyPhen [42] program are presented in bold, percentages of allele frequency are given if they differed between parental and resistant cells.

ISSN: 1479-5876