Measurement of plasma cell-free mitochondrial tumor DNA improves detection of glioblastoma in patient-derived orthotopic xenograft models

Mair, Richard
Mouliere, Florent
Smith, Christopher G
Chandrananda, Dineika
Gale, Davina
Marass, Francesco
Tsui, Dana W Y
Massie, Charles E
Wright, Alan J
Watts, Colin
Rosenfeld, Nitzan
Brindle, Kevin M

Open link

Publication date

January 2019

DOI

10.1158/0008-5472.can-18-0074

Publisher

American Association for Cancer Research (AACR)

Abstract

The factors responsible for the low detection rate of cell-free tumor DNA (ctDNA) in the plasma of glioblastoma (GB) patients are currently unknown. In this study, we measured circulating nucleic acids in patient-derived orthotopically implanted xenograft (PDOX) models of GB (n=64) and show that tumor size and cell proliferation, but not the integrity of the blood-brain barrier or cell death, affect the release of ctDNA in treatment naïve GB PDOX. Analysis of fragment length profiles by shallow genome-wide sequencing (<0.2x coverage) of host (rat) and tumor (human) circulating DNA identified a peak at 145 bp in the human DNA fragments, indicating a difference in the origin or processing of the ctDNA. The concentration of ctDNA correlated wi...