Detection of Human c-Myc and EGFR Amplifications in Circulating Extracellular Vesicles in Mouse Tumour Models

Leonora Balaj; Fatemeh Momen-Heravi; Weilin Chen; Sarada Sivaraman; Xuan Zhang; Nicole Ludwig; Eckart Meese; Thomas Wurdinger; David Noske; Alain Charest; Fred H. Hochberg; Peter Vandertop; Johan Skog; Winston Patrick Kuo

doi:10.33393/jcb.2014.2047

Authors

Leonora Balaj These authors contributed equally
Fatemeh Momen-Heravi These authors contributed equally
Weilin Chen Departments of Neurology and Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA, USA
Sarada Sivaraman Departments of Neurology and Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA, USA
Xuan Zhang Departments of Neurology and Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA, USA
Nicole Ludwig Department of Human Genetics, Medical School, Saarland University, Homburg-Saar, Germany
Eckart Meese Department of Human Genetics, Medical School, Saarland University, Homburg-Saar, Germany
Thomas Wurdinger Department of Neurosurgery, Amsterdam Cancer Center, Amsterdam, Netherlands
David Noske Department of Neurosurgery, Amsterdam Cancer Center, Amsterdam, Netherlands
Alain Charest Molecular Oncology Research Institute, Tufts University, Boston MA, USA
Fred H. Hochberg Departments of Neurology and Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA, USA
Peter Vandertop Department of Neurosurgery, Amsterdam Cancer Center, Amsterdam, Netherlands
Johan Skog Exosome Diagnostics Inc., Cambridge, MA, USA
Winston Patrick Kuo IES Diagnostics, Cambridge, MA, USA

DOI:

https://doi.org/10.33393/jcb.2014.2047

Keywords:

Cancer, Epidermoid Carcinoma, Extracellular Vesicles, Medulloblastoma, Biomarkers, Microvesicles, Gene Amplification

Abstract

Essentially, all cells release extracellular vesicles (EVs) that end up in biofluids, including blood, and the contents of these EVs can provide a window into the status of the cells from which they are released. This is particularly interesting in cancer, since these EVs allow for ‘ex-vivo’ analysis of the properties of the tumours without the need for biopsy. Gene mutations, rearrangements, amplifications, and epigenetic changes in the transcriptome can be monitored in circulating EVs. In this study, we used two human tumour cell lines derived from an epidermoid carcinoma and a medulloblastoma, which had amplification for the epidermal growth factor receptor (EGFR) and c-Myc genes, respectively. Cells were implanted subcutaneously into immunocompromised mice, and levels of gene amplification in both groups of subcutaneous tumours were quantified. We then determined if elevated levels of transcripts for the human EGFR and c-Myc were represented in circulating EVs in tumour-bearing mice. The expression levels of both human EGFR (h-EGFR) and human c-Myc (h-c-Myc) mRNAs in circulating EVs correlated well with their amplified status in the tumours. This data provides further support to the idea that circulating EVs are a potential platform for tumour biomarkers.