Mutation patterns of epidermal growth factor receptor gene in non-small cell lung cancer among Egyptian patients

Figures & data

Table 1. Mutations investigated in the four exons (18, 19, 20, 21) of EGFR gene

Number	Exon	Nucleotide change	Amino acid change
1	Exon 18	c .2156 G > C	p.G 719A
2		c.2155 G > T	p.G719C
3		c.2155 G > A	p.G719S
4	Exon 19	c.2233 2247del	p.K745_E749del
5		c.2235–2249del	p.E746_A750del
6		c.2235–2248delinsAATTC	p.E746_A750de linslP
7		c.2236–2250del	p.E746-A750 del
8		c.2235–2251delinsAATTC	p.E746_T751delinslP
9		c.2236–2253del	p.E746_T751del
10		c.2237–2251del	p.E746-T751 delinsA
11		c.2237–2252delinsT	p.E746_T751delinsV
12		c.2237–2253delinsTTGCT	p.E746_T751delinsVA
13		c.2235–2255delinsAAT	p.E746_S752delinsl
14		c.2237–2254del	p.E746_S752delinsA
15		c.2237–2255de linsT	p.E746_S752de linsV
16		c.2238–2255del	p.E746_S752delins Q
17		c.2237–2257delinsTCT	p.E746_P753delinsVS
18		c.2239–2247del	p.L747_E749del
19		c.2238–2248delinsGC	p.L747_A750delinsP
20		c.2239–2248delinsC	p.L747_A75 0delinsP
21		c.2239–2251delinsC	p.L747_T751delinsP
22		c.2240–2251del	p.L747_T751delinsS
23		c.2240–2254del?	p.L747_T751del
24		c.2239–2256del	p.L747_S752del
25		c.2239–2256delinsCAA	p.L747_S752delins Q
26		c.2239–2258delinsCA	p.L747_P753delins Q
27		c.2240–2257del	p.L747_P753delinsS
28	Exon 20	c.2369 C > T	p.T790M
29	Exon 21	c.2573 T > G	p.L858R
30		c.2582 T > A	p.L861Q

Table 2. Characteristics of the patients and control groups

Patients’ Characteristics	NSCLC Patients N = 120	Control Group N = 20	P-value
Age Mean ± S.E ≤60 years >60 years	62.7 ± 1 51 (42.5%) 69 (57.5%)	58.9 ± 1.5 12 (60%) 8 (40%)	0.33
Gender Male Female	33 (27.5%) 87 (72.5%)	10 (50%) 10 (50%)	0.043*
Tobacco smoking status Smokers Nonsmokers	38 (31.7%) 82 (68.3%)	0 (0%) 20(100%)	0.003*
Smoking status/Gender Smokers/Male – Smokers/ Female Nonsmokers/Male – Nonsmokers/Female	25(75%)-13(15%) 8(24%)- 74(85%)		0.000*
Disease status Early non-Metastatic Advanced Metastatic	55 (45.8%) 65 (54.2%)
Smoking status/Disease status Smokers/non-Metas. – Smokers/ Metas. Nonsmokers/non-Metas. – Nonsmokers/ Metas.	18(33%)-20(31%) 37(67%)-45(69%)		0.486
Tumor size 1 2 3 4 Unknown	1 (0.8%) 29 (24.2%) 23 (19.2%) 62 (51.7%) 5 (4.2%)
Stage II III IV	20 (16.7%) 18 (15%) 82 (68.3%)
Grade 2 3	96 (80%) 24 (20%)
EGFR genotype Mutant Wild-type (non-mutated)	49 (40.8%) 71 (59.1%)	0 (0%) 20 (100%)	0.013*

*Significant difference at P ≤ 0.05.

Table 3. Clinicopathological characteristics of NSCLC patients in relation to EGFR mutation status, N = 120 patients

Patients’ Characteristics	EGFR–Positive N = 49	EGFR-Negative N = 71	P-value
Age Mean ± S.E ≤60 years >60 years	61.82 ± 1.7 22 (44.9%) 27 (55.1%)	63.31 ± 1.3 29 (40.8%) 42 (59.2%)	0.709
Gender Male Female	14 (28.6%) 35 (71.4%)	19 (26.8%) 52 (73.2%)	0.827
Tobacco smoking status Smokers Nonsmokers	19 (38.8%) 30 (61.2%)	19 (26.8%) 52 (73.2%)	0.164
Disease status Early non-Metastatic Advanced Metastatic	6 (12.2%) 43 (87.8%)	49 (69%) 22 (31%)	0.000*
Tumor size 1 2 3 4 Unknown	1 (2%) 8 (16.3%) 10 (20.4%) 28 (57.1%) 2 (4.1%)	0 (0%) 21 (29.6%) 13 (18.3%) 34 (47.9%) 3 (4.2%)	0.392
Stage II III IV	3 (6.1%) 8 (16.3%) 38 (77.6%)	17 (23.9%) 10 (14.1%) 44 (62%)	0.036*
Grade 2 3	35 (71.4%) 14 (28.6%)	61 (85.9%) 10 (14.1%)	0.05*

*Significant difference at P ≤ 0.05.

Table 4. The frequencies and percentages of detected mutations in each exon of EGFR gene in NSCLC patients

Mutant EGFR Genotype	Frequency and percentage in EGFR mutation positive patients (N = 49)	Frequency and percentage in male patients (N = 14)	Frequency and percentage in female patients (N = 35)	P-value
Exon 18 mutation	5 (10.2%)	2 (6.1%)	3 (3.4%)	0.814
Exon 19 mutation	27 (55.1%)	7 (21.2%)	20 (23%)	0.879
Exon 20 mutation	4 (8.2%)	2 (6.1%)	2 (2.3%)	0.591
Exon 21 mutation	13 (26.5%)	3 (9.1%)	10 (11.5%)	0.854

P-value by comparing EGFR mutations in male with female patients.

Figure 1. Flow diagram of the study showing the enrolled groups and the detected mutated exons in EGFR gene. As shown; 120 NSCLC patients and 20 control group were enrolled in the study. 49/120 of NSCLC patients have mutated EGFR with high incidence mutations in exon 19, 21,18 and 20. No mutations were detected in the control group. EGFR, epidermal growth factor receptor; NSCLC, non-small-cell lung cancer.

Table 5. Frequencies and percentages of different mutations in each mutated exon in EGFR mutation positive patients (N = 49)

Exon	Nucleotide change	Amino acid change	Frequency and percentage of EGFR mutation positive patients (N = 49)
Exon 18	c .2156 G > C	p.G 719A	2 (4.1%)
	c.2155 G > A	p.G719S	3 (6.1%)
Exon 19	c.2240_2257del	p.L747_Pro753delins	9 (18.4%)
	c.2237–2251 del	p.E746-T751 delinsA	1 (2%)
	c.2239–2248 delins C	p.L747_Ala750delins	5 (10.2%)
	c.2240–2254 del	p.L747-T751 del	3 (6.1%)
	c.2236–2250 del	p.E746-A750 del	6 (12.2%)
	c.2235–2249 del	p.E746-A750 del	3 (6.1%)
Exon 20	c.2369 C > T	p.T790M	4 (8.2%)
Exon 21	c.2573 T > G	p.L858R	11 (22.4%)
	c.2582 T > A	p.L8610	2 (4.1%)

Figure 2. The frequencies of each somatic mutation detected in EGFR exons; 18, 19, 20 and 21 in NSCLC patients (N = 49). L858R mutation in exon 21 and L747-P753 mutation in exon 19 showed the highest incidence of all mutations, followed by E746-A750 and L747-A750 mutations in exon 19. The other mutations have low rate of incidence. EGFR, epidermal growth factor receptor; NSCLC, non-small-cell lung cancer.