DNA From Cerebrospinal Fluid May Effectively Monitor Brain Metastases

cerebrospinal fluid
cerebrospinal fluid
Researchers found that brain tumor mutations could be detected from ctDNA in cerebrospinal fluid.

Sequencing DNA from cerebrospinal fluid may be a more effective method of detecting and characterizing genomic alterations in brain tumor metastases than sequencing DNA from plasma, according to research published in Nature Communications.

Examining metastases in the brain is challenging given the restrictive and invasive access for sampling the tumor, as well as the difficulty of accurately understanding the full tumor’s DNA with only a small tissue sample.

Recent studies have shown that cell-free circulating tumor DNA (ctDNA) in blood plasma could be used to characterize and monitor tumors, but ctDNA analysis of patients with brain tumors has revealed that brain tumor DNA either does not show up in plasma, or is only found in very low levels.

The aim of the research by Leticia de Mattos-Arruda, MD, from the Vall d’Hebron Institute of Oncology in Barcelona, Spain and colleagues was to determine whether analyzing ctDNA from cerebrospinal fluid would be more useful in detecting and accurately characterizing and monitoring metastases in the brain. To do this, the researchers obtained tumor samples and sequenced tumor DNA from 12 patients: 4 with glioblastomas, 6 with brain metastases from breast cancer, and 2 with brain metastases from lung cancer.

The researchers found that ctDNA from cerebrospinal fluid was more representative of brain tumor genomic alterations than ctDNA from plasma, and putative actionable gene mutations and copy-number alterations, specifically EGFR, PTEN, ESR1, IDH1, ERBB2, and FGFR2, could be identified. They also observed that ctDNA from cerebrospinal fluid has a significantly higher sensitivity for central nervous system genomic alterations compared with plasma, and can be used to detect brain tumor mutations and to monitor tumor progression.

The researchers also found that ctDNA from cerebrospinal fluid may complement the diagnosis of leptomeningeal carcinomatosis.

This procedure is much less invasive than traditional methods of obtaining samples of brain tumor tissues, and could lead to changes in the way brain metastases are detected, monitored, and treated.

“The identification of the brain metastasis-specific genomic alterations through CSF ctDNA might facilitate the design of tailored treatments to target brain metastasis, hopefully increasing the clinical response of these deadly lesions,” the authors wrote.

“In a context where the oncology field expects that therapeutic approaches will be dictated and guided by the genomic features of tumors, the presence of CSF ctDNA will be fundamental to the correct molecular diagnosis and treatment of brain tumors,” they concluded.


  1. De Mattos-Arruda L, Mayor R, Ng CKY, et al. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nat Commun. 2015; doi:10.1038/ncomms9839.