DETECTING EGFR MUTATIONS IN PATIENTS
WITH NON-SMALL CELL LUNG CANCER Hammoudeh ZA, Antonova O, Staneva R, Nikolova D, Kyuchukov Y,
Penev A, Mintchev T, Koleva V, Hadjidekova S, Toncheva D *Corresponding Author: Zora A. Hammoudeh, Molecular Biologist, Department of Medical Genetics, Medical University Sofia,
2 Zdrave Str., 1431 Sofia, Bulgaria. Tel: +359-2-917-2735. Mobile: +359-88-943-0505. E-mail: zorahammoudeh@yahoo.com page: 13
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DISCUSSION
In our study, exon 19 deletions and the point mutation
L858R in exon 21 constituted 92.7% of all EGFR gene
mutations, which confirms the findings of previous studies
[11]. Deletions in exon 19 of the EGFR gene were detected
in 56.3% (n = 31) of all mutated samples, while L858R was
detected in 36.4% (n = 20). All the EGFR gene exon 19
deletions positive patients had stage IV cancer. The L858R
mutation was found in 36.4% (n = 20) of EGFR positive
cases, with 90.0% (n = 18) having stage IV and 10.0% (n
= 2) stage IIIb. Insertions in exon 20 represented 3.6%
(n = 2) of all detected mutations. The rarest cases in our
cohort, in concordance with previously reported results in
the literature, were the double mutants, representing 3.6%
(n = 2). A T790M point mutation was detected in only one
sample together with a deletion in exon 19. In the other
double mutant sample, a combination of a S768I mutation
and a deletion in exon 19 was detected.
According to smoking status, there was a higher
prevalence of the EGFR gene mutation positive cases in
smokers. In our cohort, the EGFR gene mutations were
found in 15.0% (n = 32) patients who had never smoked
and in 6.8% (n = 23) smokers (p <0.003).
The prevalence of the EGFR gene mutations was
higher in females than in males. Female to male ratio in
the EGFR gene mutation positive cases in our cohort was
2.4:1, with 27.1% (n = 39) positive cases in female samples
and 3.9% (n = 16) in males (p <0.001). The frequency
of the mutations in adenocarcinomas was higher than in other histological types with a statistically different (14.9
vs. 5.1%, p <0.001) frequency.
Multiple studies have shown that mutations in the
EGFR gene TK domain are used as predictors for the therapeutic
response and the progression-free survival benefit
of EGFR treatment [12]. Many studies showed that EGFR
gene mutations are more common in adenocarcinomas in
women and non smokers [13]. Our results are consistent
with previous studies.
Our results showed that 10.0% of the advanced
NSCLC patients in Bulgaria carried mutations in the EGFR
gene. The statistical analysis showed the difference in
EGFR gene mutation rate between female and male patients
to be statistically significant (p <0.001). Likewise,
the analysis showed the difference in EGFR gene mutation
rate between patients with adenocarcinomas and patients
with other histological types (such as squamous cell carcinoma
and large cell carcinoma) to be significant (p =
0.0001). Whereas the results showed the difference in
EGFR gene mutation rate between non smoking patients
and patients who smoked to be statistically significant (p
<0.003).
In our cohort, exon 19 deletions and the L858R mutation
represented 92.7% of the detected mutations conveying
sensitivity to TKIs. Deletion in the EGFR gene exon
19 was found in 23 lung adenocarcinomas, eight in other
histological types. The L858R EGFR gene mutation was
found in 16 lung adenocarcinomas, four in other histological
types. The remaining 7.3% of the mutations we
detected are insertions in exon 20 and double mutations,
exon 19 deletion and T790M, and exon 19 deletion and
S768I. The EGFR gene exon 19 deletion and S768I double
mutation was detected in lung adenocarcinoma, and the
EGFR gene exon 19 deletion and T790M double mutation
was found in a squamous cell carcinoma. The EGFR
gene exon 20 insertions were found in two samples, one
lung adenocarcinoma and one squamous cell carcinoma.
Previous studies have shown that NSCLC patients
whose tumors have sensitive mutation in the EGFR gene
respond better than those with a wild-type tumor variant
to drugs that target the TK domain of the gene. Therefore,
according to all therapeutic guidelines, it is mandatory
to determine the mutational status of the EGFR gene in
patients with NSCLC in order to assess their eligibility for
TKI treatment [14,15]. The EGFR gene exon 19 deletions
and L858R mutation convey sensitivity to first-generation
EGFR TKIs [8]. The T790M mutation predicts resistance
to first-generation EGFR TKIs.
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