Exosome-based detection of activating and resistance EGFR mutations from plasma of non-small cell lung cancer patients
Article
Castellanos-Rizaldos, E, Zhang, X, Tadigotla, VR et al. (2019). Exosome-based detection of activating and resistance EGFR mutations from plasma of non-small cell lung cancer patients
. 10(30), 2911-2920. 10.18632/oncotarget.26885
Castellanos-Rizaldos, E, Zhang, X, Tadigotla, VR et al. (2019). Exosome-based detection of activating and resistance EGFR mutations from plasma of non-small cell lung cancer patients
. 10(30), 2911-2920. 10.18632/oncotarget.26885
Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer and its molecular landscape has been extensively studied. The most common genetic alterations in NSCLC are mutations within the epidermal growth factor receptor (EGFR) gene, with frequencies between 10-40%. There are several molecular targeted therapies for patients harboring these mutations. Liquid biopsies constitute a flexible approach to monitor these mutations in real time as opposed to tissue biopsies that represent a single snap-shot in time. However, interrogating cell free DNA (cfDNA) has inherent biological limitations, especially at early or localized disease stages, where there is not enough tumor material released into the patient's circulation. We developed a qPCR- based test (ExoDx EGFR) that interrogates mutations within EGFR using Exosomal RNA/DNA and cfDNA (ExoNA) derived from plasma in a cohort of 110 NSCLC patients. The performance of the assay yielded an overall sensitivity of 90% for L858R, 83% for T790M and 73% for exon 19 indels with specificities of 100%, 100%, and 96% respectively. In a subcohort of patients with extrathoracic disease (M1b and MX) the sensitivities were 92% (L858R), 95% (T790M), and 86% (exon 19 indels) with specificity of 100%, 100% and 94% respectively.
