Towards standardization of next-generation sequencing of FFPE samples for clinical oncology: intrinsic obstacles and possible solutions

Table 1 Identified exonic mutations in non-EGFR genes

Gene	Protein sequence variation	Patient	Tumor histology	Mutant allele frequency (%)	Variant impact
HNF1A	p.Gly306 fs	5	LUAD	15	Deleterious
TP53	p.Gly272 fs	9	LUAD	15	Deleterious
TP53	p.Val173Met	10	LUAD	17	Deleterious [40]
MLH1	p.Ser406Asn	12	LUAD	15	Deleterious [41]
KIT	p.Glu76Asp	12	LUAD	50	Unknown
TP53	p.Leu206_Arg209del	12	LUAD	70	Unknown
ABL1	p.Thr243Ile	65	LUAD	15	Unknown
KRAS	p.Gly12Cys	65	LUAD	31	Activated
CTNNB1	p.Ser33Phe	89	LUAD	11	Activated [42]
KRAS	p.Gly12Asp	90	LUAD	30	Activated
TP53	p.Cys238Tyr	91	LUSC	44	Deleterious [40]
NOTCH1	p.Leu1600Pro	105	LUSC	11	Activated [43]
TP53	p.Arg175 fs	106	LUSC	56	Deleterious
HRAS	p.Gly13Val	120	LUSC	82	Activated [44]
AKT1	p.Glu17Lys	120	LUSC	4	Activated [45]
TP53	p.Ser215Gly	131	LUSC	45	Deleterious [40]
ATM	p.Asn856Ile	140	LUSC	10	Unknown
TP53	p.His214Arg	150	LUSC	33	Deleterious [40]
TP53	p.Arg337Pro	152	LUSC	50	Deleterious [40]
VHL	p.Lys171Arg	161	NSCLC	18	Deleterious [46, 47]
TP53	p.Arg248Gln	161	NSCLC	31	Deleterious [48, 49]
TP53	p.Ser185 fs	187	NSCLC	17	Deleterious
RB1	p.Ser576 fs	187	NSCLC	18	Deleterious
PIK3CA	p.Glu545Lys	193	NSCLC	15	Activated [50, 51]
TP53	p.Tyr205Asp	193	NSCLC	22	Deleterious [40]

Synonymous variants, common polymorphisms (KDR p.Q472H, KIT p.M541L, TP53 p.P72R, HNF1A p.G226A) as well as presumably germline variants (ATM p.F858L) are not shown. Frameshift and nonsense variants were accounted as deleterious
For variant annotation, the following references were used: ABL1—NP_005148.2; AKT1—NP_005154.2; ATM—NP_000042.3; BRAF—NP_004324.2; CTNNB1—NP_001091679.1; EGFR—NP_005219.2; HNF1A—NP_000536.5; HRAS—NP_001123914.1; KDR—NP_002244.1; KIT—NP_000213.1; KRAS—NP_004976.2; MLH1—NP_000240.1; NOTCH1—NP_060087.3; PIK3CA—NP_006209.2; RB1—NP_000312.2; STK11—NP_000446.1; TP53—NP_000537.3; VHL—NP_000542.1
LUAD lung adenocarcinoma, LUSC squamous cell lung carcinoma, NSCLC non-small cell lung cancer of unknown or mixed histology

ISSN: 1479-5876