Exosome-based detection of activating and resistance EGFR mutations from plasma of non-small cell lung cancer patients
2019
// Elena Castellanos-Rizaldos 1 , * , Xuan Zhang 1 , * , Vasisht R. Tadigotla 1 , Dominik G. Grimm 2 , Chris Karlovich 3 , Luis E. Raez 4 and Johan K. Skog 1 1
ExosomeDiagnostics, a Bio-
Technebrand, Waltham, Massachusetts, USA 2
ExosomeDiagnostics, a Bio-
Technebrand, Martinsried, Germany 3 Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA 4 Memorial Cancer
Institute,
MemorialHealth Care System, Florida International University, Florida, USA * These authors contributed equally to this work Correspondence to: Johan K. Skog, email: johan.skog@bio-techne.com Keywords:
liquid biopsy;
exosomes; ctDNA; exoNA; NSCLC Received: February 06, 2019 Accepted: April 07, 2019 Published: April 23, 2019 ABSTRACT 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 biopsiesconstitute 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 diseasestages, 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
ExosomalRNA/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
T790Mand 73% for exon 19
indelswith 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.
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