Worldwide Frequency of Commonly Detected EGFR Mutations

Abstract

Context.-Recurrent epidermal growth factor receptor (EGFR) mutations are seen in a subset of pulmonary adenocarcinomas. These mutations are targeted by EGFR inhibitors and are a biomarker for response to EGFR inhibitor therapies. Initial data have indicated an increased frequency of activating EGFR mutations in nonsmoking Asian females. However, there are very few studies of global scope that address the question of mutation distribution across the population of lung cancer.Objective.-To determine the frequency of EGFR mutations in exons 18 through 21 detected in clinical laboratories participating in the College of American Pathologists proficiency testing program for EGFR in calendar year 2013.Design.-We reviewed the surveys from 170 clinical laboratories from 20 countries that participated in the College of American Pathologists EGFR proficiency testing program. The proficiency testing includes questions regarding the total numbers of tests performed at each common mutation site, including both activating and resistance mutations, and their frequency. Countries were grouped into regional groups in order to assess frequency of mutation by type, and to indirectly assess ethnic differences in mutation frequencies.Results.-Among the treatment-sensitive activating mutations, the most common are exon 19 mutations (n ¼ 10 802 of 136 533 cases; 7.9% of total cases tested) and the exon 21 L858R mutation (n ¼ 10 351 of 136 533 cases; 7.6% of total cases tested) and the least common are exon 20 mutations (n ¼ 466 of 136 533 cases; 0.3% of total cases tested). The T790M mutation in exon 20 is the more common resistance mutation (n ¼ 1010 of 136 533 cases; 0.7% of all cases tested). The highest activating mutation frequency is seen in southern Asia (n ¼ 4260 of 9337 cases; 46%) and the lowest activating mutation frequencies are in South and North America (n ¼ 113 of 1439 cases and 7926 of 86 654 cases; 8% and 9%, respectively).Conclusions.-Our data confirm that activating EGFR mutations are more common in southern Asia and that the distribution of activating EGFR mutations varies significantly across the regions. Similarly, the frequency and distribution of resistance mutations also show significant variation when comparing southern Asia with other regions.

Status of 10 targeted genes of non‐small cell lung cancer in eastern China: A study of 884 patients based on NGS in a single institution

“…To the best of our knowledge, somatic mutations of EGFR are more common in Asian patients. 14 In our study, the frequency of EGFR mutations was higher than previous reports in Chinese NSCLC cohorts, 15,16 but was similar to recent studies. 17,18 This may be due to an improvement in medical level and detection methods, whereby more patients are diagnosed in early stage disease which improves the positive detection rate.…”

Comprehensive analysis of HPV infection, EGFR exon 20 mutations and LINE1 hypomethylation as risk factors for malignant transformation of sinonasal‐inverted papilloma to squamous cell carcinoma

“…This discrepancy might be due to different tumour series analysed. Indeed, it remains unclear if EGFR mutation incidences in sinonasal epithelial tumours could have strikingly different distributions based on geographical areas, as occurs in lung cancer . Secondly, the potential of local aggressiveness of EGFR wild‐type ISPs, could be deeply investigating by a comprehensive analysis of MAPK and PI3K/AKT/mTOR pathways in the subset of EGFR wild‐type ISP.…”

Molecular Diagnostic of Solid Tumor Using a Next Generation Sequencing Custom-Designed Multi-Gene Panel

“…The samples were analyzed using a panel customized for specific genomic regions including 128 amplicons (dual strand) for a total of 256 amplicons (15.04 kb; median amplicons size: 130 bp). The panel includes 58 target regions in the following 22 genes (human reference sequence hg19/GRCh37): BRAF (exon 15), c-Kit (exons 8,9,11,13,17), CTNNB1 (exon 3), EGFR (exons 12,18,19,20,21), EIF1AX (exons 1, 2), GNAS (exons 8, 9), H3F3A (exon 1), HRAS (exons 2, 3), IDH1 (exon 4), IDH2 (exon 4), KRAS (exons 2, 3, 4), MED12 (exon 2), MET (exon 2, 14), NRAS (exons 2, 3, 4), PDGFRα (exons 12, 14, 18), PIK3CA (exons 10, 21), PTEN (exon 5), RET (exons 5,8,10,11,13,15,16), RNF43 (exons 2, 8), SMAD4 (exons 6,9,10,11,12), TERT (promoter region, g.1295141-g.1295471), and TP53 (exons 4, 5,6,7,8,9).…”

“…The genes evaluated depend on clinical guidelines and on the specific needs for treatment and diagnostic purposes as defined in the integrated care pathways for each tumor type of a given medical center (see "Results" section). To this point, mutations considered "pathogenic" were evaluated according to data reported in well-established mutation databases (e.g., COSMIC database [1], ClinVar https://www.ncbi.nlm.nih.gov/clinvar/, My Cancer Genome https://www.mycancergenome.org/) and following the recommendations of accepted guidelines [2][3][4][5][6][7][8][9][10][11][12]. Synonymous mutations not falling in a splicing site or well-known SNPs were considered "benign" mutations.…”