scholarly journals Analytical Validation of a Pan-Cancer Panel for Cell-Free Assay for the Detection of EGFR Mutations

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1022
Author(s):  
Min-Kyung So ◽  
Jong-Ho Park ◽  
Jong-Won Kim ◽  
Ja-Hyun Jang
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Reference Materials ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Advanced Lung Cancer ◽  
Clinical Samples ◽  
Lung Cancer Patients ◽  
Pan Cancer

Liquid biopsies have increasingly shown clinical utility. Although next-generation sequencing has been widely used for the detection of somatic mutations from plasma, performance characteristics vary by platform. Therefore, thorough validation is mandatory for clinical use. This study aimed to evaluate the analytical validity of the Oncomine Pan-Cancer Cell-Free Assay. A massively parallel sequencing for the assay was performed using the Ion S5 XL System with Ion 540 kit. The analytical sensitivity and precision were evaluated using pre-characterized reference materials. The specificity was evaluated using plasma from healthy subjects. A comparison with the Cobas EGFR Mutation Test v2 was performed using reference materials and plasma from lung cancer patients. For SNVs and short indels, the analytical sensitivities at variant allele frequencies (VAFs) of 0.1%, 0.5%, and 1% were 50%, 93.4%, and 100% with 20 ng of input, respectively. The overall precision of the true positive variants was 98% at a VAF of 1% with 20 ng input. The assay showed a similar sensitivity to that of the Cobas EGFR Mutation Test v2 at a VAF of 0.5% with 20 ng of input and 100% concordance on clinical samples. The Pan-Cancer Cell-Free Assay can be applied to detect EGFR mutations in advanced lung cancer patients, although follow-up studies will be needed to evaluate the analytical validity for other types of genes and aberrations using clinical samples.

Epidemiology of PD-L1 and ALK expression and EGFR mutational status in Argentinian patients with lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20565-e20565 ◽  
Author(s):  
Ruben Salanova ◽  
Julio C Calderazzo Pereyra ◽  
Laura Leguina ◽  
Asuncion Bena ◽  
Mariana Barberis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Alk Rearrangement ◽  
Lung Cancer Patients ◽  
Mutational Status ◽  
Alk Positive ◽  
Egfr Mutant ◽  
Exon 19

e20565 Background: Until now, the results of the correlation between PD-L1, ALK expression and EGFR mutations remain controversial. We prospectively evaluated patterns among EGFR mutant, ALK positive and PD-L1 positive lung cancer patients. Methods: PD-L1 and ALK expression was evaluated in 342 adenocarcinomas (AD) of the lung using inmunohistochemestry (anti-PD-L1 22C3, anti-ALK D5F3), and EGFR mutations using real time PCR (therascreen EGFR RGQ PCR Kit version 2). PD-L1 was also evaluated in 36 squamous (SQ) cell carcinomas. Results: 181 of 342 patients with AD were positive for PD-L1. 108 were positive with a TPS value between 1 and 49, and 73 were positive with a TPS value higher than 50 (p = 0.002). 25 of 36 patients with SQ were positive for PD-L1. 17 were positive with a TPS value between 1 and 49, and 8 were positive with a TPS value higher than 50. 133 samples with AD PD-L1 positive and 97 PD-L1 negative were tested for EGFR and ALK, 33 and 14 respectively were positive for EGFR mutations (p = 0.15), with 45% for exon 19 deletions (p = 0.003), 5 and 0 respectively were positive for ALK translocations (p = 0.053). 210 of 342 patients were men and 132 were women, 117 and 64 were positive for PD-L1 expression respectively (p > 0.1). Conclusions: NSCLC with EGFR mutation showed a trend for higher frequency of positive PD-L1 expression and NSCLC harboring ALK rearrangement was significantly associated with PD-L1 expression. These findings might contribute to the understanding of the regulation of PD-L1 expression in lung cancer and its relation to ALK expression and EGFR mutation.

The mutation profile of EGFR in resectable Chinese lung cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20519-e20519
Author(s):  
Wenjun Mao ◽  
Ruo Chen ◽  
Jingyu Chen ◽  
Feng Liu ◽  
Yijun He ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Therapy ◽  
Cancer Patients ◽  
Egfr Mutation ◽  
Disease Stage ◽  
Advanced Lung Cancer ◽  
Clinicopathological Factors ◽  
Lung Cancer Patients ◽  
Mutation Profile ◽  
Egfr Tkis

e20519 Background: The frequency of EGFR mutation in Asian advanced lung cancer patients is about 40% and the application of EGFR tyrosine kinase inhibitors (TKIs) has become a standard treatment therapy. Several studies showed that usage of EGFR TKIs in adjuvant or neo-adjuvant therapy was promising, while the mutation profile of EGFR mutations in resectable Chinese lung cancer patients was still scanty. Our study investigated EGFR mutation profile and its correlation with clinicopathological factors. Methods: 343 resectable patients with lung cancer were selected for eligibility criteria, and tumor tissues were collected for gene detection. EGFR genetic testing was performed by amplification refractory mutation system PCR (ARMS-PCR) with specific sensitive mutation sites. The clinicopathological factors of study population were recorded based on pre-design protocol. Chi-square or fish exact test were used to statistic analysis Results: A total of 343 patients were enrolled in study. 42.6% (146/343) patients were male, 20.4% (68/333) patients were smokers, the adenocarcinoma accounted for 93.8 % (319/340), and stage 0, I, II, III was 7.3% (25/343), 68.8% (236/343), 8.5% (29/343), 15.5% (53/343), respectively. The frequency of EGFR mutation was 54.2% (186/343) in whole population, and the proportion of EGFR L858R, 19Del, 719X, 768I, 861Q mutation was 31.2% (107/343), 21.3% (73/343), 1.2% (4/343), 1.0% (3/343), 1.0% (3/343), respectively. 1.2% (4/343) patients presented EGFR co-mutation (EGFR G719X/S768I; L858R/S768I; G719X/S768I; L858R/L861Q) .The mutation frequency of EGFR mutation was associated with sex, smoking, differentiation, pathology (P = 0.0076, < 0.0001, < 0.0001, < 0.0001, respectively). In subgroup analysis, the incidence of two main mutation types, EGFR L858R and 19del, were associated with disease stage (P = 0.044) and age (P = 0.035). Conclusions: EGFR mutation in resectable lung cancer was a common phenomenon as advanced stage and our study might provide useful informations for using EGFR-TKIs in further adjuvant or neo-adjuvant therapy.

Determination of plasma EGFR mutations from non-small cell lung cancer patients at Bach Mai Hospital.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13121-e13121
Author(s):  
Cam Phuong Pham ◽  
Khoa Trong Mai ◽  
Nguyen Thuan Loi ◽  
NGO Thi Thu Hien ◽  
Quynh Thi Thuy Vo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Lung Cancer Patients

e13121 Background: Lung cancer patients with mutations in the epidermal growth factor receptor (EGFR) are primary candidates for EGFR-targeted therapy. Reliable analyses of such mutations have previously been possible only in tumor tissue. Here, we demonstrate that mutations can be detected in plasma samples of non-small cell lung cancer patients at Bach Mai Hospital and relation of different variables to the frequency of EGFR mutations. Methods: 193 patients with non-small cell lung cancer were identified with EGFR mutation by cobas EGFR Mutation Test v2 kit (Roche Diagnostics, USA), evaluating the EGFR mutation status with different variables. Results: The EGFR mutation rate was 43%, common in patients with adenocarcinoma, female, non-smoking, late stage disease. The rate of EGFR T790M mutation was 36.1%. Among 78 patients who was previous treated TKIs, EGFR mutation rate was 73.1% and the rate of EGFR T790M mutation was 50.8% at the time of progression. The concordance of EGFR mutation from plasma sample with tissue sample was 81%. Conclusions: EGFR mutation in plasma sample results was not different from those in tissue samples and similar with result of studies in Vietnam and worldwide.

scholarly journals Application of a Cancer Hotspot Panel to Guide Lung Cancer Therapy: Asian Experience

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 35s-35s
Author(s):  
M.-L. Nairismägi ◽  
K.-C. Tung ◽  
Y.-T. Yang ◽  
Y.-J. Lu ◽  
R.-S. Jhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Resistance Mechanisms ◽  
Genetic Alterations ◽  
Egfr Mutations ◽  
Clinical Samples ◽  
Lung Cancer Patients ◽  
Domain Identification ◽  
Base Substitutions ◽  
Tki Resistance

Background: Comprehensive genomic profiling (CGP) has transformed personalized medicine but is still not affordable to all patients, especially in developing countries. The price of CGP differs based on panel size. Aim: The aim of this study was to explore the benefits between a cancer hotspot panel and CGP in Asian lung cancer patients. Methods: One hundred sixty-two formalin-fixed, paraffin-embedded (FFPE) lung cancer clinical samples were subjected to next-generation sequencing using the Ion Torrent Proton System. Sixty-six cases were profiled using a 35-gene cancer hotspot panel and 96 with pathway-based CGP (400+ genes) for base substitutions (single nucleotide variants and small indels) and copy number variants (CNV). Results: In total, actionable variants were discovered in 86.4% (57/66) cases using the cancer hotspot panel, with 57.9% (33/57) derived from base substitutions, 10.5% (6/57) from CNVs and 31.6% (18/57) from both alterations. Contrarily, CGP identified actionability in 97.9% (94/96) patients, 17.0% (16/94) of which were from base substitutions, 22.3% (21/94) from CNVs and 60.6% (57/94) from both. EGFR mutations were identified in comparable frequency with both panels, with almost half (48.8%; 79/162) of all samples harboring activating mutations in the tyrosine kinase (TK) domain. Identification of EGFR TK inhibitor (TKI) resistance mechanisms, including EGFR mutations (T790M and C797S), EGFR amplification, abnormal downstream EGFR signaling ( KRAS, BRAF and PIK3CA mutations, PTEN loss) and activation of the bypass pathways ( MET amplification, HER2 mutation and amplification), was equivalent with both panels. Additional targetable genetic alterations were detected in 70.0% (21/30) and 83.3% (39/47) of EGFR-wild type patients using the cancer hotspot assay and CGP, respectively. Conclusion: In most Asian lung cancer patients, a cancer hotspot panel is sufficient to discover targetable genetic alterations and TKI resistance mechanisms.

TP53 Exon 8 Mutations are Associated with Shorter Survival in Advanced Lung Cancer Patients

2018 ◽  
Author(s):  
Yutao Liu ◽  
Fang Xu ◽  
Yubo Wang ◽  
Qingchen Wu ◽  
Buhai Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Advanced Lung Cancer ◽  
Lung Cancer Patients
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