1. Detection of genes mutations in cerebrospinal fluid circulating tumor DNA from neoplastic meningitis patients using next generation sequencing.
- Author
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Zhao Y, He JY, Cui JZ, Meng ZQ, Zou YL, Guo XS, Chen X, Wang X, Yan LT, Han WX, Li C, Guo L, and Bu H
- Subjects
- Acrylamides administration & dosage, Adult, Aged, Aniline Compounds administration & dosage, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Circulating Tumor DNA cerebrospinal fluid, Class I Phosphatidylinositol 3-Kinases genetics, Crown Ethers administration & dosage, Crown Ethers adverse effects, Female, Genes, erbB-1, Humans, Karnofsky Performance Status, Lung Neoplasms cerebrospinal fluid, Lung Neoplasms drug therapy, Male, Meningeal Neoplasms genetics, Meningeal Neoplasms secondary, Middle Aged, Mutation Rate, Proto-Oncogene Proteins c-akt genetics, Quinazolines administration & dosage, Quinazolines adverse effects, Young Adult, Circulating Tumor DNA genetics, DNA Copy Number Variations, High-Throughput Nucleotide Sequencing, Lung Neoplasms genetics, Meningeal Neoplasms cerebrospinal fluid, Mutation
- Abstract
Background: 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)., Methods: A 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., Results: The 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., Conclusions: This 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.
- Published
- 2020
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