A nanowire-based liquid biopsy method using cerebrospinal fluid cell-free DNA for targeted management of leptomeningeal carcinomatosis

Author(s):  
Wonyoung Choi ◽  
Youngnam Cho ◽  
Seog-Yun Park ◽  
Kum Hui Hwang ◽  
Ji-Youn Han ◽  
...  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Zimeng Ye ◽  
Zac Chatterton ◽  
Jahnvi Pflueger ◽  
John A Damiano ◽  
Lara McQuillan ◽  
...  

Abstract Brain somatic mutations are an increasingly recognized cause of epilepsy, brain malformations and autism spectrum disorders and may be a hidden cause of other neurodevelopmental and neurodegenerative disorders. At present, brain mosaicism can be detected only in the rare situations of autopsy or brain biopsy. Liquid biopsy using cell-free DNA derived from cerebrospinal fluid has detected somatic mutations in malignant brain tumours. Here, we asked if cerebrospinal fluid liquid biopsy can be used to detect somatic mosaicism in non-malignant brain diseases. First, we reliably quantified cerebrospinal fluid cell-free DNA in 28 patients with focal epilepsy and 28 controls using droplet digital PCR. Then, in three patients we identified somatic mutations in cerebrospinal fluid: in one patient with subcortical band heterotopia the LIS1 p. Lys64* variant at 9.4% frequency; in a second patient with focal cortical dysplasia the TSC1 p. Phe581His*6 variant at 7.8% frequency; and in a third patient with ganglioglioma the BRAF p. Val600Glu variant at 3.2% frequency. To determine if cerebrospinal fluid cell-free DNA was brain-derived, whole-genome bisulphite sequencing was performed and brain-specific DNA methylation patterns were found to be significantly enriched (P = 0.03). Our proof of principle study shows that cerebrospinal fluid liquid biopsy is valuable in investigating mosaic neurological disorders where brain tissue is unavailable.


2019 ◽  
Vol 14 (5) ◽  
pp. 924-932 ◽  
Author(s):  
Mei-Mei Zheng ◽  
Yang-Si Li ◽  
Ben-Yuan Jiang ◽  
Hai-Yan Tu ◽  
Wen-Fang Tang ◽  
...  

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi112-vi112
Author(s):  
Jun-ichi Adachi ◽  
Tomonari Suzuki ◽  
Kazuhiko Mishima ◽  
Ryo Nishikawa

2017 ◽  
Vol 135 (1) ◽  
pp. 29-36 ◽  
Author(s):  
Ian David Connolly ◽  
Yingmei Li ◽  
Wenying Pan ◽  
Eli Johnson ◽  
Linya You ◽  
...  

Author(s):  
Suman Kumar Ray ◽  
Sukhes Mukherjee

: Cell-free DNA (cfDNA) is present in numerous body fluids in addition to initiates generally from blood cells. It is undoubtedly the utmost promising tool among all components of liquid biopsy. Liquid biopsy is a specialized method investigating the nonsolid biological tissue by revealing of circulating cells, cell free DNA etc. that enter body fluids. Since, cancer cells disengage from compact tumors circulate in peripheral blood, evaluating blood of cancer patients holds the opportunities for capture and molecular level analysis of various tumor-derived constituents. Cell free DNA samples can deliver a significant perceptions into oncology, for instance tumor heterogeneity, instantaneous tumor development, response to therapy and treatment, comprising immunotherapy and mechanisms of cancer metastasis. Malignant growth at any phase can outhouse tumor cells in addition to fragments of neoplasticity causing DNA into circulatory system giving noble sign of mutation in the tumor at sampling time. Liquid biopsy distinguishes diverse blood based evolving biomarkers comprising circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or cfDNA, circulating RNA (cfRNA) and exosomes. Cell free DNA are little DNA fragments found circulating in plasma or serum, just as other fluids present in our body. Cell free DNA involves primarily double stranded nuclear DNA and mitochondrial DNA, present both on a surface level and in the lumen of vesicles. The probable origins of the tumor-inferred portion of cfDNA are apoptosis or tumor necrosis, lysis of CTCs or release of DNA from the tumor cells into circulation. The evolution of innovations, refinement and improvement in therapeutics for determination of cfDNA fragment size and its distribution provide significant information related with pathological conditions of the cell, thus emerging as promising indicator for clinical output in medical biotechnology.


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