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

Autor: Litian Yan, Yue Li Zou, Hui Bu, Li Guo, Xin Chen, Chunyan Li, Zi-Qi Meng, Xueliang Wang, Wei Xin Han, Xiao Su Guo, Jun Zhao Cui, Yue Zhao, Jun Ying He
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Cancer Research
Lung Neoplasms
Circulating Tumor DNA
0302 clinical medicine
Mutation Rate
CDKN2A
Crown Ethers
Meningeal Neoplasms
Copy-number variation
Aniline Compounds
biology
High-Throughput Nucleotide Sequencing
Neoplastic meningitis
PI3K-Akt pathway
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Cancer-associated genes mutations
Oncology
030220 oncology & carcinogenesis
Cerebrospinal fluid ctDNA
Female
GNAQ
Research Article
Adult
DNA Copy Number Variations
Class I Phosphatidylinositol 3-Kinases
Antineoplastic Agents
MLH1
lcsh:RC254-282
Young Adult
03 medical and health sciences
Next generation sequencing
Genetics
medicine
Humans
PTEN
Karnofsky Performance Status
Gene
PI3K/AKT/mTOR pathway
Aged
Acrylamides
Genes
erbB-1
medicine.disease
Molecular biology
030104 developmental biology
Mutation
Quinazolines
biology.protein
Proto-Oncogene Proteins c-akt
Zdroj: BMC Cancer, Vol 20, Iss 1, Pp 1-17 (2020)
BMC Cancer
DOI: 10.21203/rs.2.16237/v3
Popis: 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.
Databáze: OpenAIRE
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