scholarly journals Detection of epidermal growth factor receptor mutation in lung cancer by droplet digital polymerase chain reaction

2015 ◽  
pp. 1533 ◽  
Author(s):  
Qing Xu ◽  
Mao Mao ◽  
Guangjuan Zheng ◽  
Yazhen Zhu ◽  
Xirun Zheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Polymerase Chain Reaction ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Chain Reaction ◽  
Epidermal Growth ◽  
Polymerase Chain ◽  
Digital Polymerase Chain Reaction

scholarly journals Exosomes as a biomarker platform for detecting epidermal growth factor receptor–positive high-grade gliomas

2018 ◽  
Vol 128 (4) ◽  
pp. 1091-1101 ◽  
Author(s):  
Sasidhar Venkata Manda ◽  
Yogesh Kataria ◽  
Babul Reddy Tatireddy ◽  
Balasubramaniam Ramakrishnan ◽  
Boola Gnana Ratnam ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
High Grade ◽  
Chain Reaction ◽  
Epidermal Growth ◽  
Polymerase Chain ◽  
Paired Serum

OBJECTIVEHigh-grade glial brain tumors are often characterized by an elevated expression of the tumorigenic epidermal growth factor receptor variant III (EGFRvIII). The authors sought to establish a clinically adaptive protocol as a noninvasive diagnostic tool for EGFRvIII detection through serum exosomes.METHODSPurity of serum exosome/RNA was confirmed by electron microscopy and flow cytometry and through an RNA bioanalyzer profile. EGFRvIII amplification was initially established by semiquantitative polymerase chain reaction in tumor tissues and exosomes. Diagnostic performance of EGFRvIII transcript in tissue versus exosome was determined using a 2 × 2 clinical table approach. Overall survival was determined using Kaplan-Meier analysis.RESULTSThe EGFRvIII transcript was detected in 39.5% of tumor tissue samples and in 44.7% of their paired serum exosome samples; 28.1% of biopsy tumors coexpressed wild-type EGFR and EGFRvIII. Tissue EGFRvIII amplification served as the reference-positive control for its paired serum expression. The overall clinical sensitivity and specificity of semiquantitative exosome EGFRvIII polymerase chain reaction detection assay in serum were 81.58% (95% CI 65.67%–92.26%) and 79.31% (95% CI 66.65%–88.83%), respectively. Age, sex, tumor location, and side of the body on which the tumor was located had no effect on the detection rate of exosomal EGFRvIII transcript. EGFRvIII expression either in exosomes or tissue correlated with poor survival.CONCLUSIONSThe authors established a serum-based method for detection of EGFRvIII in high-grade brain tumors that might serve as an optimal noninvasive method for diagnosing EGFRvIII-positive high-grade gliomas.

scholarly journals Heterogeneity and Coexistence of T790M and T790 Wild-Type Resistant Subclones Drive Mixed Response to Third-Generation Epidermal Growth Factor Receptor Inhibitors in Lung Cancer

2018 ◽  
pp. 1-15 ◽  
Author(s):  
Zofia Piotrowska ◽  
Mehlika Hazar-Rethinam ◽  
Coleen Rizzo ◽  
Brandon Nadres ◽  
Emily E. Van Seventer ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Third Generation ◽  
Chain Reaction ◽  
Liquid Biopsies ◽  
Epidermal Growth ◽  
Polymerase Chain ◽  
Digital Polymerase Chain Reaction

Purpose Third-generation epidermal growth factor receptor (EGFR) inhibitors like nazartinib are active against EGFR mutation–positive lung cancers with T790M-mediated acquired resistance to initial anti-EGFR treatment, but some patients have mixed responses. Methods Multiple serial tumor and liquid biopsies were obtained from two patients before, during, and after treatment with nazartinib. Next-generation sequencing and droplet digital polymerase chain reaction were performed to assess heterogeneity and clonal dynamics. Results We observed the simultaneous emergence of T790M-dependent and -independent clones in both patients. Serial plasma droplet digital polymerase chain reaction illustrated shifts in relative clonal abundance in response to various systemic therapies, confirming a molecular basis for the clinical mixed radiographic responses observed. Conclusion Heterogeneous responses to treatment targeting a solitary resistance mechanism can be explained by coexistent tumor subclones harboring distinct genetic signatures. Serial liquid biopsies offer an opportunity to monitor clonal dynamics and the emergence of resistance and may represent a useful tool to guide therapeutic strategies.

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