학술논문

Cell-free DNA and circulating TERT promoter mutation for disease monitoring in newly-diagnosed glioblastoma
Document Type
Clinical report
Source
Acta Neuropathologica Communications. November 4, 2020, Vol. 8 Issue 1
Subject
DNA -- Genetic aspects
Glioblastomas -- Care and treatment -- Genetic aspects -- Development and progression
Language
English
ISSN
2051-5960
Abstract
The clinical implications of plasmatic cell-free and tumor DNA (cfDNA and ctDNA) are challenging in glioblastoma. This prospective study included 52 consecutive newly diagnosed glioblastoma (n = 49) or gliosarcoma (n = 3) patients treated with concomitant temozolomide and radiotherapy (RT-TMZ), followed by a TMZ maintenance phase. Plasma samples were collected at baseline, before RT-TMZ (pre-RT-TMZ) and at the end of adjuvant TMZ, or at the time of progression in cases of progressive disease (PD). The cfDNA concentration was measured with a fluorometric method, and ctDNA was detected using targeted droplet digital PCR. The main objectives were to analyze the associations between cfDNA and ctDNA measurements during the course of treatment with PD and survival. There was a significant decrease in median cfDNA concentration from baseline to pre-RT-TMZ--19.4 versus 9.7 ng/mL (p < 0.0001)--in the entire cohort. In patients with PD, a significant increase in cfDNA concentration from pre-RT-TMZ to time of PD was observed, from 9.7 versus 13.1 ng/mL (p = 0.037), respectively, while no difference was observed for nonprogressive patients. Neither the cfDNA concentration at baseline nor its kinetics correlated with survival. ctDNA was detected in 2 patients (3.8%) and only in gliosarcoma subtypes. Trial registration ClinicalTrial, NCT02617745. Registered 1 December 2015, https://clinicaltrials.gov/ct2/show/NCT02617745?term=glioplak&draw=2&rank=1. Keywords: Glioblastoma, Cell-free DNA, Circulating tumor DNA, TERT promoter mutation, Liquid biopsy
Author(s): Maxime Fontanilles[sup.1,2,10], Florent Marguet[sup.3,4], Ludivine Beaussire[sup.1], Nicolas Magne[sup.5], Louis-Ferdinand Pépin[sup.6], Cristina Alexandru[sup.2], Isabelle Tennevet[sup.2], Chantal Hanzen[sup.7], Olivier Langlois[sup.8], Fabrice Jardin[sup.3], Annie Laquerrière[sup.3,4], Nasrin Sarafan-Vasseur[sup.1], Fréderic Di Fiore[sup.1,2,9] and Florian [...]