Cerebrospinal fluid circulating tumor DNA depicts profiling of brain metastasis in NSCLC

Jun Wu, Zhiqiang Liu, Tianxiang Huang, Ying Wang, Meng Meng Song, Tao Song, Gretchen Long, Xiaobing Zhang, Xi Li, Longbo Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Brain metastasis (BM) genetically diverges from the primary tumor in non-small-cell lung cancer (NSCLC). Hence, accurately capturing clinically relevant alterations is pivotal for the delivery of targeted therapies. Circulating tumor DNA (ctDNA) sequencing has emerged as a promising liquid biopsy in the biomarker-based clinical management of recurrent and extracranial metastatic NSCLC. However, the absence of simultaneous sequencing data from brain metastatic sites prevents the definitive evaluation of the efficacy of ctDNA in representing genetic profiles in BM. Here, we performed parallel genomic comparisons between matched BM and primary tumor DNA, plasma ctDNA, and cerebrospinal fluid (CSF) ctDNA. The results indicated that CSF ctDNA had a greater ability than plasma ctDNA to comprehensively represent the mutational landscape of BM, with CSF ctDNA detecting all BM mutations in 83.33% of patients, while plasma ctDNA was only 27.78%. Mutant allele frequency (MAF) in CSF ctDNA was highly correlated with the tumor size of BM (r = 0.95), and the mean MAF in CSF ctDNA was higher than that in plasma ctDNA (38.05% vs. 4.57%, respectively). MAF and tumor mutational burden in CSF ctDNA were strongly associated with those in BM (r = 0.96 and 0.97, respectively). Of note, CSF ctDNA had significantly higher concordance with BM than plasma ctDNA (99.33% vs. 67.44%), facilitating the identification of clinically relevant mutations. Moreover, we found that plasma ctDNA has stronger profiling performance, with a concordance of 93.01% in multiple brain metastases, equivalent to CSF ctDNA. Collectively, our study indicates that CSF ctDNA is superior to plasma ctDNA in accurately representing the profiling of single BM. Plasma ctDNA could be an alternative liquid biopsy material to be applied in multiple brain metastatic NSCLC.

Original languageEnglish
JournalMolecular Oncology
DOIs
Publication statusE-pub ahead of print - 10 Dec 2022

Bibliographical note

Funding Information: This work was supported by Hunan Natural Science Foundation of China 2019JJ40516 (JW).

Publisher Copyright: © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Fingerprint

Dive into the research topics of 'Cerebrospinal fluid circulating tumor DNA depicts profiling of brain metastasis in NSCLC'. Together they form a unique fingerprint.

Cite this