Detection of genes mutations in cerebrospinal fluid circulating tumor DNA from neoplastic meningitis patients using next generation sequencing

Yue Zhao,Xin Chen,Xueliang Wang,Jun Zhao Cui,Jun Ying He,Li Guo,Hui Bu,Wei Xin Han,Li-Tian Yan,Xiao Su Guo,Yue Li Zou,Zi-Qi Meng,Chunyan Li

doi:10.1186/s12885-020-07172-x

Abstract

BackgroundThis study profiled the somatic genes mutations and the copy number variations (CNVs) in cerebrospinal fluid (CSF)-circulating tumor DNA (ctDNA) from patients with neoplastic meningitis (NM).MethodsA total of 62 CSF ctDNA samples were collected from 58 NM patients for the next generation sequencing. The data were bioinformatically analyzed by (Database for Annotation, Visualization and Integrated Discovery) DAVID software.ResultsThe most common mutated gene was TP53 (54/62; 87.10%), followed by EGFR (44/62; 70.97%), PTEN (39/62; 62.90%), CDKN2A (32/62; 51.61%), APC (27/62: 43.55%), TET2 (27/62; 43.55%), GNAQ (18/62; 29.03%), NOTCH1 (17/62; 27.42%), VHL (17/62; 27.42%), FLT3 (16/62; 25.81%), PTCH1 (15/62; 24.19%), BRCA2 (13/62; 20.97%), KDR (10/62; 16.13%), KIT (9/62; 14.52%), MLH1 (9/62; 14.52%), ATM (8/62; 12.90%), CBL (8/62; 12.90%), and DNMT3A (7/62; 11.29%). The mutated genes were enriched in the PI3K-Akt signaling pathway by the KEGG pathway analysis. Furthermore, the CNVs of these genes were also identified in these 62 samples. The mutated genes in CSF samples receiving intrathecal chemotherapy and systemic therapy were enriched in the ERK1/2 signaling pathway.ConclusionsThis study identified genes mutations in all CSF ctDNA samples, indicating that these mutated genes may be acted as a kind of biomarker for diagnosis of NM, and these mutated genes may affect meningeal metastasis through PI3K-Akt signaling pathway.

Highlights

This study profiled the somatic genes mutations and the copy number variations (CNVs) in cerebrospinal fluid (CSF)-circulating tumor DNA from patients with neoplastic meningitis (NM)
This study identified genes mutations in all CSF circulating tumor DNA (ctDNA) samples, indicating that these mutated genes may be acted as a kind of biomarker for diagnosis of Neoplastic meningitis (NM), and these mutated genes may affect meningeal metastasis through PI3K-Akt signaling pathway
A total of 62 CSF samples were collected from these 58 NM patients, in which three CSF samples were collected from a single patient, while two CSF samples were collected from other two patients at distinct time points

Summary

Introduction

This study profiled the somatic genes mutations and the copy number variations (CNVs) in cerebrospinal fluid (CSF)-circulating tumor DNA (ctDNA) from patients with neoplastic meningitis (NM). The present study aimed to investigate the gene mutations in the CSF ctDNA samples obtained from NM patients using the cutting-edge technique of generation sequencing (NGS). This approach can help to characterize NM genetic profiles and profile of gene mutations, which can thereby be potentially applied for molecularly targeted therapy. Towards this end, a recent study [8] genetically profiled the CSF ctDNA obtained from NM patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Characterization of gene mutations in CSF ctDNA samples can provide valuable clinical guidance for precision medicine

Methods

Results

Discussion

Conclusion