Blood-Based Detection of BRAF V600E in Gliomas and Brain Tumor Metastasis

Abstract

Liquid biopsy provides a minimally invasive platform for the detection of tumor-derived information, including hotspot mutations, such as BRAF V600E. In this study, we provide evidence of the technical development of a ddPCR assay for the detection of BRAF V600E mutations in the plasma of patients with glioma or brain metastasis. In a small patient cohort (n = 9, n = 5 BRAF V600E, n = 4 BRAF WT, n = 4 healthy control), we were able to detect the BRAF V600E mutation in the plasma of 4/5 patients with BRAF V600E-tissue confirmed mutant tumors, and none of the BRAF WT tumors. We also provide evidence in two metastatic patients with longitudinal monitoring, where the plasma-based BRAF V600E mutation correlated with clinical disease status. This proof of principle study demonstrates the potential of this assay to serve as an adjunctive tool for the detection, monitoring, and molecular characterization of BRAF mutant gliomas and brain metastasis.

Management of Inoperable Supra-Sellar Low-Grade Glioma With BRAF Mutation in Young Children

“…These findings need to be validated in prospective clinical trials. Liquid biopsies have the potential to detect multiple types of mutations commonly found in PLGGs, including those positive for the BRAF-V600E mutation [2,[6][7][8]. This diagnostic technique has multiple advantages, including being non-invasive, able to summarize the entire genetic makeup of the tumor, and providing quantitative information that can be trended over time and correlated with treatment response [2,[6][7][8].…”

“…Liquid biopsies have the potential to detect multiple types of mutations commonly found in PLGGs, including those positive for the BRAF-V600E mutation [2,[6][7][8]. This diagnostic technique has multiple advantages, including being non-invasive, able to summarize the entire genetic makeup of the tumor, and providing quantitative information that can be trended over time and correlated with treatment response [2,[6][7][8]. However, important disadvantages associated with fluid biopsies in PLGGs include the lower level of sensitivity demonstrated by current assays and variability in the sensitivity levels between the various types of biofluids used for this technique [2,8].…”

“…To date, there are very limited features on currently available neuroimaging techniques (computed tomography [CT], magnetic resonance imaging [MRI], and other imaging methods) that can reliably predict a specific molecular diagnosis. This has prompted the emergence of liquid biopsies from biologic samples such as peripheral blood and cerebrospinal fluid (CSF) [2,[6][7][8]. These biofluids may contain material released from cancer cells, including circulating tumor DNA (ctDNA), that can be tested for known PLGG-associated mutations [2,[6][7][8].…”

“…This has prompted the emergence of liquid biopsies from biologic samples such as peripheral blood and cerebrospinal fluid (CSF) [2,[6][7][8]. These biofluids may contain material released from cancer cells, including circulating tumor DNA (ctDNA), that can be tested for known PLGG-associated mutations [2,[6][7][8]. This non-invasive method has the potential to play a crucial role in diagnosing PLGGs, providing molecular characteristics of the tumor, monitoring response to treatment, and detecting disease progression [2,[6][7][8].…”

“…These biofluids may contain material released from cancer cells, including circulating tumor DNA (ctDNA), that can be tested for known PLGG-associated mutations [2,[6][7][8]. This non-invasive method has the potential to play a crucial role in diagnosing PLGGs, providing molecular characteristics of the tumor, monitoring response to treatment, and detecting disease progression [2,[6][7][8]. In this report, we describe a toddler with a large supra-sellar mass that progressed on chemotherapy but demonstrated a significant and sustained reduction on dabrafenib, leading to an almost complete clinical and radiological This case report was presented at the 19th International Symposium on Pediatric Neuro-Oncology, ISPNO-2020, Karuizawa, Nagano, Japan.…”