The different clinical significance of EGFR mutations in exon 19 and 21 in non-small cell lung cancer patients of China

Abstract

Mutations of epithelial growth factor receptor (EGFR) in exon 19 and 21 are both believed to be associated with carcinogenesis, sensitivity to tyrosine kinase drugs and with the prognosis of non-small cell lung cancers (NSCLCs). However, their exact clinical significance remains disputable. We detected the mutations of 157 NSCLCs from mainland China with high resolution melting analysis and identified exon mutations with DNA sequencing. Of the 157 cases examined, 57 displayed EGFR mutations which included 22 in exon 19 and 35 in exon 21. Current research has shown that EGFR mutations are more commonly associated with the female population and East Asians, with additional significance being adenocarcinomas. Our current findings are supporting this sugestion. We analysed the clinicalpathological characteristics of mutations in exon 19 and 21 separately, which showed that the mutation frequency of NSCLCs in exon 21, but not in exon 19, were significantly higher in females. Comparatively, mutation frequencies in exon 19 were significantly higher in the stage I and II than in the stage III abnd IV, while tumors with lymph node metastasis and the stage III and IV demonstrated significantly higher mutation frequencies in exon 21. Additionally, exon mutations in the left and right lung showed significant differences: with exon 19 mutations being more frequent in the tumors of left lung, and exon 21 mutuations showing a higher incidence in right lung tumors. This suggests that, in mainland China, NSCLCs with EGFR mutations in exon 19 could have a less malignant character than those with mutations in exon 21. It's the first report that EGFR mutations in exon 19 and exon 21 in NSCLC patients may relate to the tumor sites, but further research is still required.

Lack of Mutations in Protein Tyrosine Kinase Domain Coding Exons 19 and 21 of the EGFR Gene in Oral Squamous Cell Carcinomas

“…This observation in OSCC is in contrast to those that have been reported in NSCLCs, wherein 48% to 83% and 43% to 67% of tumor samples were found to carry exon 19 and 21 mutations respectively (Pao et al, 2004;Gazdar, 2009;Li et al, 2011). Mutations in these two exons have also been observed in triple negative breast cancer at a frequency of 1.4-11.4% (Weber et al, 2005;Generali, 2007;Teng et al, 2011) and at a frequency of 7.3% in laryngeal cancers (Lee et al, 2006).…”

“…While copy number amplification and activating truncated mutations (EGFRvlll) have been observed in OSCCs, exon mutations as those that occur in NSCLCs or triple negative breast cancers have not yet been reported. In order to address this issue, we investigated the genomic DNA obtained from OSCC tissues for the status of exon 19 and 21 of EGFR as these regions have been shown to be frequently mutated in other cancers (Marchetti et al, 2005;Li et al, 2011;Peraldo-Neia et al, 2011;Teng et al, 2011). Direct sequencing analysis of the PCR amplicons revealed absence of mutation in any of the forty OSCC samples that were analyzed.…”

Relationship between Epidermal Growth Factor Receptor Gene Mutations and Clinicopathological Features in Patients with Non-Small Cell Lung Cancer in Western Turkey

“…When compared with wild-types, mutation positive cases demonstrate better prognosis, while prognosis and survival rates differ according to exon mutation sites (Jackman et al, 2006;Li et al, 2011;Sun et al, 2011). Exon 20 mutation was associated with a poor prognosis, while exon 19, and 21 mutations were correlated with a good prognosis, and longer survival (Jackman et al, 2006;Li et al, 2011;Sun et al, 2011). At the same time, exon 19, and 21 mutations were found to be robust predictors of improved response rates for anti-EGFR treatments, on the contrary, exon 20 mutation was reported as an inducer of resistance to therapy.…”

Genotyping Accuracy of High-Resolution DNA Melting Instruments

“…Highresolution melting is widely used in research and clinical diagnostics for detecting DNA sequence variants, either known (genotyping) or unknown (scanning). Most single nucleotide variants (SNVs), 4 as well as most small deletions or insertions, are easily genotyped, often resulting in reduced costs and sequencing burden for many analyses (5)(6)(7)(8)(9). Heterozygotes introduce large shape changes in the melting curves and are easy to detect, with accuracies approaching 100% (10 ).…”