Oncotarget

Research Papers:

Exosome-based detection of activating and resistance EGFR mutations from plasma of non-small cell lung cancer patients

Elena Castellanos-Rizaldos, Xuan Zhang, Vasisht R. Tadigotla, Dominik G. Grimm, Chris Karlovich, Luis E. Raez and Johan K. Skog _

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Oncotarget. 2019; 10:2911-2920. https://doi.org/10.18632/oncotarget.26885

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Abstract

Elena Castellanos-Rizaldos1,*, Xuan Zhang1,*, Vasisht R. Tadigotla1, Dominik G. Grimm2, Chris Karlovich3, Luis E. Raez4 and Johan K. Skog1

1 Exosome Diagnostics, a Bio-Techne brand, Waltham, Massachusetts, USA

2 Exosome Diagnostics, a Bio-Techne brand, Martinsried, Germany

3 Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA

4 Memorial Cancer Institute, Memorial Health 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 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.


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