Multiple mutations in the EGFR gene in patients diagnosed with lung cancer.

Abstract

e20542 Background: Lung cancer is the most common malignant tumor after breast cancer and is the main cause of cancer mortality. Mutations in the EGFR gene typical of lung cancer lead to constitutive activation of the epidermal growth factor receptor and malignant cell transformation. The purpose of this study was to identify associations between double and triple mutations in EGFR and clinical and pathological characteristics of patients in the South of Russia diagnosed with lung cancer. Methods: DNA was extracted from FFPE samples of 240 patients. Mutations in EGFR were detected using Cobas EGFR Mutation Test detection kit (Roche). Results: The mutant type of EGFR was identified in 24.6% of cases, and the most common activating mutations were ex19del (47.5%) and L858R (30.5%). Insertion in exon 20 was detected in 5.1% of mutation cases, G719X - in 3.4%. We also registered cases of identification of two or three mutations in one tumor: ex19del - L858R, ex19del - T790M, L858R - T790M with a frequency of 3.4% and G719X - ex20ins, ex19del - L858R - ex20ins with a frequency of 1.7%. Similar frequency is characteristic of the Caucasoid population of the USA. Multiple mutations in EGFR are associated with early manifestations of lung cancer and rapid progression of the disease. Two patients with two mutations EGFR T790M and L858R were of particular interest. According to the literature data, T790M is the most common somatic mutation that causes resistance to targeted therapy; however, rare cases could be associated with germinal variation of T790M. The primary T790M mutation is more common in patients with two or three mutations in EGFR. Conclusions: Mutations in the EGFR gene were detected in 24.6% of lung cancer cases in a patient population in the South of Russia. The frequency of two or three mutations in the EGFR gene was 0.33%. The timely detection of these mutations is particularly important for family cases when the risk group can be determined.

The role of oncogenes and tumor suppressor genes in determining survival rates of lung cancer patients in the population of North Sumatra, Indonesia

“…In the previous studies, the double mutations consisted of exon 20 T790M, which has been identified as primary factors in 1 st and 2 nd EGFR TKI-resistance. 38 Barnet et al also showed shorter PFS in a patient with co-mutations of exon 19 with noncommon EGFR mutations including exon 20, T90M, and PIK3CA. 39 This differs from the current study, which looked at exon 19 and exon 21 mutations.…”

“…The various studies tried to identify the impact of double mutations or triple mutations of EGFR in clinicopathology characteristics in lung cancer patients. 37,38 All previous studies showed poorer outcomes with multiple mutations compared with single EGFR mutations. 37,38 Nevertheless, in this study, double mutations of exon 19 and exon 21 showed a better outcome in both OS and PFS compared with single mutations of exon 19.…”

“…37,38 All previous studies showed poorer outcomes with multiple mutations compared with single EGFR mutations. 37,38 Nevertheless, in this study, double mutations of exon 19 and exon 21 showed a better outcome in both OS and PFS compared with single mutations of exon 19. Unfortunately, this study was a small size study, so it is still difficult to draw general conclusions concerning the wider population.…”

Case of inherited epidermal growth factor receptor (EGFR) in non-small cell lung carcinoma (NSCLC) in a 37-year-old male

“…When two or three mutations in one tumor is seen with combination of for example ex19del-ex20ins with the T790M, the frequency is at 1.7% Overall, the frequency of having two-three gene mutations in EGFR is 0.33% so it is especially rare. 7 There are other mutations rarer in the exon 18-25 that tend to reflect poor prognosis. 8 About 10% of nonsmall cell lung cancers respond well with tyrosine kinase inhibitors (TKIs) that target EGFR.…”