Evaluating the cerebrospinal fluid ctDNA detection by next-generation sequencing in the diagnosis of meningeal Carcinomatosis
Abstract Background Meningeal carcinomatosis (MC) is the most severe form of brain metastasis and causes significant morbidity and mortality. Currently, the diagnosis of MC is routinely confirmed on the basis of clinical manifestation, positive cerebrospinal fluid (CSF) cytology, and/or neuroimaging...
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doaj-1490fcc425224abfaa636d66983119b92020-12-20T12:17:25ZengBMCBMC Neurology1471-23772019-12-011911910.1186/s12883-019-1554-5Evaluating the cerebrospinal fluid ctDNA detection by next-generation sequencing in the diagnosis of meningeal CarcinomatosisYue Zhao0Jun-Ying He1Yue-Li Zou2Xiao-Su Guo3Jun-Zhao Cui4Li Guo5Hui Bu6Department of Neurology, The Second Hospital of Hebei Medical UniversityDepartment of Neurology, The Second Hospital of Hebei Medical UniversityDepartment of Neurology, The Second Hospital of Hebei Medical UniversityDepartment of Neurology, The Second Hospital of Hebei Medical UniversityDepartment of Neurology, The Second Hospital of Hebei Medical UniversityDepartment of Neurology, The Second Hospital of Hebei Medical UniversityDepartment of Neurology, The Second Hospital of Hebei Medical UniversityAbstract Background Meningeal carcinomatosis (MC) is the most severe form of brain metastasis and causes significant morbidity and mortality. Currently, the diagnosis of MC is routinely confirmed on the basis of clinical manifestation, positive cerebrospinal fluid (CSF) cytology, and/or neuroimaging features. However, negative rate of CSF cytology and neuroimaging findings often result in a failure to diagnose MC from the patients who actually have the disease. Here we evaluate the CSF circulating tumor DNA (ctDNA) in the diagnosis of MC. Methods A total of 35 CSF samples were collected from 35 patients with MC for CSF cytology examination, CSF ctDNA extraction and cancer-associated gene mutations detection by next-generation sequencing (NGS) at the same time. Results The most frequent primary tumor in this study was lung cancer (26/35, 74%), followed by gastric cancer (2/35, 6%), breast cancer (2/35, 6%), prostatic cancer (1/35, 3%), parotid gland carcinoma (1/35, 3%) and lymphoma (1/35, 3%) while no primary tumor could be found in the remaining 2 patients in spite of using various inspection methods. Twenty-five CSF samples (25/35; 71%) were found neoplastic cells in CSF cytology examination while all of the 35 CSF samples (35/35; 100%) were revealed having detectable ctDNA in which cancer-associated gene mutations were detected. All of 35 patients with MC in the study underwent contrast-enhanced brain MRI and/or CT and 22 neuroimaging features (22/35; 63%) were consistent with MC. The sensitivity of the neuroimaging was 88% (95% confidence intervals [95% CI], 75 to 100) (p = 22/25) and 63% (95% CI, 47 to 79) (p = 22/35) compared to those of CSF cytology and CSF ctDNA, respectively. The sensitivity of the CSF cytology was 71% (95% CI, 56 to 86) (n = 25/35) compared to that of CSF ctDNA. Conclusions This study suggests a higher sensitivity of CSF ctDNA than those of CSF cytology and neuroimaging findings. We find cancer-associated gene mutations in ctDNA from CSF of patients with MC at 100% of our cohort, and utilizing CSF ctDNA as liquid biopsy technology based on the detection of cancer-associated gene mutations may give additional information to diagnose MC with negative CSF cytology and/or negative neuroimaging findings.https://doi.org/10.1186/s12883-019-1554-5Meningeal CarcinomatosisCerebrospinal fluid ctDNANext-generation sequencingCancer-associated gene mutations |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yue Zhao Jun-Ying He Yue-Li Zou Xiao-Su Guo Jun-Zhao Cui Li Guo Hui Bu |
spellingShingle |
Yue Zhao Jun-Ying He Yue-Li Zou Xiao-Su Guo Jun-Zhao Cui Li Guo Hui Bu Evaluating the cerebrospinal fluid ctDNA detection by next-generation sequencing in the diagnosis of meningeal Carcinomatosis BMC Neurology Meningeal Carcinomatosis Cerebrospinal fluid ctDNA Next-generation sequencing Cancer-associated gene mutations |
author_facet |
Yue Zhao Jun-Ying He Yue-Li Zou Xiao-Su Guo Jun-Zhao Cui Li Guo Hui Bu |
author_sort |
Yue Zhao |
title |
Evaluating the cerebrospinal fluid ctDNA detection by next-generation sequencing in the diagnosis of meningeal Carcinomatosis |
title_short |
Evaluating the cerebrospinal fluid ctDNA detection by next-generation sequencing in the diagnosis of meningeal Carcinomatosis |
title_full |
Evaluating the cerebrospinal fluid ctDNA detection by next-generation sequencing in the diagnosis of meningeal Carcinomatosis |
title_fullStr |
Evaluating the cerebrospinal fluid ctDNA detection by next-generation sequencing in the diagnosis of meningeal Carcinomatosis |
title_full_unstemmed |
Evaluating the cerebrospinal fluid ctDNA detection by next-generation sequencing in the diagnosis of meningeal Carcinomatosis |
title_sort |
evaluating the cerebrospinal fluid ctdna detection by next-generation sequencing in the diagnosis of meningeal carcinomatosis |
publisher |
BMC |
series |
BMC Neurology |
issn |
1471-2377 |
publishDate |
2019-12-01 |
description |
Abstract Background Meningeal carcinomatosis (MC) is the most severe form of brain metastasis and causes significant morbidity and mortality. Currently, the diagnosis of MC is routinely confirmed on the basis of clinical manifestation, positive cerebrospinal fluid (CSF) cytology, and/or neuroimaging features. However, negative rate of CSF cytology and neuroimaging findings often result in a failure to diagnose MC from the patients who actually have the disease. Here we evaluate the CSF circulating tumor DNA (ctDNA) in the diagnosis of MC. Methods A total of 35 CSF samples were collected from 35 patients with MC for CSF cytology examination, CSF ctDNA extraction and cancer-associated gene mutations detection by next-generation sequencing (NGS) at the same time. Results The most frequent primary tumor in this study was lung cancer (26/35, 74%), followed by gastric cancer (2/35, 6%), breast cancer (2/35, 6%), prostatic cancer (1/35, 3%), parotid gland carcinoma (1/35, 3%) and lymphoma (1/35, 3%) while no primary tumor could be found in the remaining 2 patients in spite of using various inspection methods. Twenty-five CSF samples (25/35; 71%) were found neoplastic cells in CSF cytology examination while all of the 35 CSF samples (35/35; 100%) were revealed having detectable ctDNA in which cancer-associated gene mutations were detected. All of 35 patients with MC in the study underwent contrast-enhanced brain MRI and/or CT and 22 neuroimaging features (22/35; 63%) were consistent with MC. The sensitivity of the neuroimaging was 88% (95% confidence intervals [95% CI], 75 to 100) (p = 22/25) and 63% (95% CI, 47 to 79) (p = 22/35) compared to those of CSF cytology and CSF ctDNA, respectively. The sensitivity of the CSF cytology was 71% (95% CI, 56 to 86) (n = 25/35) compared to that of CSF ctDNA. Conclusions This study suggests a higher sensitivity of CSF ctDNA than those of CSF cytology and neuroimaging findings. We find cancer-associated gene mutations in ctDNA from CSF of patients with MC at 100% of our cohort, and utilizing CSF ctDNA as liquid biopsy technology based on the detection of cancer-associated gene mutations may give additional information to diagnose MC with negative CSF cytology and/or negative neuroimaging findings. |
topic |
Meningeal Carcinomatosis Cerebrospinal fluid ctDNA Next-generation sequencing Cancer-associated gene mutations |
url |
https://doi.org/10.1186/s12883-019-1554-5 |
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