scholarly journals BIOM-56. THE INTEGRATION OF A LIQUID BIOPSY PROGRAM INTO THE CARE OF PEDIATRIC BRAIN TUMOR PATIENTS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii13-ii14
Author(s):  
Alexandra Miller ◽  
Luca Szalontay ◽  
Hamza Ahmad ◽  
Nancy Bouvier ◽  
Irene Rodriguez-Sanchez ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Clinical Care ◽  
High Grade Glioma ◽  
Response To Therapy ◽  
Low Grade ◽  
High Grade ◽  
Cell Free Dna ◽  
Free Dna ◽  
Minimal Residual

Abstract Pediatric CNS tumors remain the leading cause of cancer-related death in children and adolescents. Safe sampling of tumor tissue for diagnostic purposes may be difficult if not impossible. Detection of minimal residual or recurrent disease prior to definitive clinical or radiographic progression may allow earlier initiation of novel therapies and ultimately improve overall survival. Given the rarity of serial sampling of tumor tissue, our understanding of molecular evolution in response to therapy remains limited. Recent technological advances have led to the development of “liquid biopsy” assays, which detect cell-free DNA (cfDNA) in blood, cerebrospinal fluid (CSF) or other bodily fluids. Here, we report our initial clinical experience with the recently established MSK Kids pediatric neuro-oncology liquid-biopsy program at Memorial Sloan Kettering Cancer Center (MSKCC) using MSK-IMPACT, which is clinically validated by the New York State Department of Health for CSF cell-free DNA (cfDNA)vprofiling. All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families. Samples from 29 unique patients were sequenced. Histopathology included high-grade glioma (5); low-grade glioma (2); medulloblastoma (8); pineoblastoma (3); retinoblastoma (4); other (7). CSF cfDNA could be detected in 18/42 samples (43%) and 12/29 patients (34%). CSF cfDNA was more commonly detected in higher-grade, disseminated tumors such as high-grade glioma (60%), medulloblastoma (38%), and pineoblastoma (100%). Low-grade lesions without leptomeningeal involvement did not result in detectable CSF cfDNA shedding (86% were negative). In a subset of patients, MSK-IMPACT identified previously unrecognized molecular actionable targets (e.g. BRAF-KIAA1549 fusion); or the detection of “minimal residual disease” prior to the detection of tumor recurrence by conventional diagnostics, impacting clinical care decisions. Future directions include integration of CSF cfDNA into prospective clinical trials as a correlative biomarker.

Cell free DNA as an evolving liquid biopsy biomarker for initial diagnosis and therapeutic nursing in Cancer- An evolving aspect in Medical Biotechnology

2020 ◽  
Vol 21 ◽  
Author(s):  
Suman Kumar Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Tumor Cells ◽  
Liquid Biopsy ◽  
Cancer Metastasis ◽  
Nuclear Dna ◽  
Fragment Size ◽  
Body Fluids ◽  
Response To Therapy ◽  
Significant Information ◽  
Cell Free Dna ◽  
Free Dna

: 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.

scholarly journals Molecular characterisation of longitudinally collected circulating cell-free DNA in HPV+ve and HPV-ve oropharyngeal cancer

2020 ◽  
Author(s):  
John P Thomson ◽  
Sophie J Warlow ◽  
Martyna Adamowicz ◽  
Helen Thain ◽  
Kate Cuschieri ◽  
...  
Keyword(s):  
Deep Sequencing ◽  
Clinical Decision Making ◽  
Fragment Size ◽  
Clinical Care ◽  
Significant Risk ◽  
Post Treatment ◽  
Response To Therapy ◽  
Cell Free Dna ◽  
Tissue Biopsy ◽  
Free Dna

Oropharyngeal squamous cell carcinoma (OPSCC) is an increasing global health problem and is divided into two types dependent on association with human papillomavirus (HPV), with a more favourable prognosis in virus-associated tumours. Current methods of establishing viral aetiology, assessing response to therapy and clinical monitoring rest on tissue biopsy, clinical examination and post-treatment imaging. However, tissue biopsy is invasive and carries significant risk of morbidity, and post-treatment scans are frequently indeterminate. Analysis of cell-free DNA (cfDNA) from the circulation provides a minimally invasive method for detecting and monitoring cancer-derived DNA fragments, with the potential for enhancing clinical care. Through the longitudinal collection of 166 blood samples in 67 OPSCC patients we evaluate the utility of three cfDNA analysis methods: droplet digital PCR (ddPCR) and fragment size analysis in both HPV+ve and HPV-ve disease, and ultra-deep sequencing in patients with HPV-ve disease. We show that ddPCR analysis of cfDNA for five HPV types (16, 18, 31, 33 & 35) is strongly concordant with existing clinical assays (p16 immunohistochemistry (IHC) and quantitative PCR analysis of solid tumour tissue) and that cfDNA fragment size was reduced in OPSCC patients compared to healthy controls. Sequential ddPCR measurements of cfDNA HPV copy number showed a decrease to undetectable levels in all 30 HPV+ve patients in at least one of their post-treatment samples and a corresponding increase in cfDNA fragment size in patients who had a complete response to chemoradiotherapy. In two HPV+ve patients, clinical decision-making based on HPV ddPCR of cfDNA may have led to earlier detection of relapse in one patient or avoided surgical exploration in a second patient, which led to resection of tissue that did not harbour malignancy. In HPV-ve disease, ultra-deep sequencing identified tumour-derived somatic mutations of circulating cfDNA in genes such as TP53 and members of the ERBB family that are potential markers of therapeutic responsiveness and patient prognosis. Together our data suggest that analysis of circulating cfDNA can enhance current clinical strategies for assessing therapeutic response and disease monitoring in both HPV+ve and HPV-ve OPSCC.

scholarly journals HGG-09. A ROBUST CELL-FREE DNA (CFDNA) ASSAY TO DETECT MUTATIONS IN PLASMA SAMPLES OF PEDIATRIC HIGH GRADE GLIOMA PATIENTS DESPITE GENOMIC DNA (GDNA) CONTAMINATION

2019 ◽  
Vol 21 (Supplement_2) ◽  
pp. ii88-ii88
Author(s):  
Agda Karina Eterovic ◽  
Nader Ezzeddine ◽  
Ping Song ◽  
Lin-ya Tang ◽  
Mohammad Mohammad ◽  
...  
Keyword(s):  
Genomic Dna ◽  
High Grade Glioma ◽  
High Grade ◽  
Plasma Samples ◽  
Cell Free Dna ◽  
Free Dna ◽  
Gdna Contamination ◽  
Pediatric High Grade Glioma

scholarly journals Targeted Liquid Biopsy Using Irradiation to Facilitate the Release of Cell-Free DNA from a Spatially Aimed Tumor Tissue

2021 ◽  
Author(s):  
Jae Myoung Noh ◽  
Yeon Jeong Kim ◽  
Ho Yun Lee ◽  
Changhoon Choi ◽  
Won-Gyun Ahn ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Jagged Ends of Cell-Free DNA: Rebranding Fragmentomics in Modern Liquid Biopsy Diagnostics

2021 ◽  
Vol 67 (4) ◽  
pp. 576-578
Author(s):  
Margaritis Avgeris ◽  
Antonios Marmarinos ◽  
Dimitrios Gourgiotis ◽  
Andreas Scorilas
Keyword(s):  
Liquid Biopsy ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Cerebrospinal fluid liquid biopsy for detecting somatic mosaicism in brain

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Zimeng Ye ◽  
Zac Chatterton ◽  
Jahnvi Pflueger ◽  
John A Damiano ◽  
Lara McQuillan ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Liquid Biopsy ◽  
Somatic Mutations ◽  
Somatic Mosaicism ◽  
Autism Spectrum ◽  
Brain Diseases ◽  
Cell Free Dna ◽  
Free Dna ◽  
Subcortical Band Heterotopia ◽  
Fluid Cell

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.

scholarly journals A multiparametric extraction method for Vn96-isolated plasma extracellular vesicles and cell-free DNA that enables multi-omic profiling

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeremy W. Roy ◽  
Catherine A. Taylor ◽  
Annie P. Beauregard ◽  
Surendar R. Dhadi ◽  
D. Craig Ayre ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Liquid Biopsy ◽  
Small Rna Sequencing ◽  
Isolation Method ◽  
Protein Biomarkers ◽  
Cell Free Dna ◽  
Extraction Protocol ◽  
Free Dna ◽  
Rich Material ◽  
Short Timeframe

AbstractExtracellular vesicles (EVs) have been recognized as a rich material for the analysis of DNA, RNA, and protein biomarkers. A remaining challenge for the deployment of EV-based diagnostic and prognostic assays in liquid biopsy testing is the development of an EV isolation method that is amenable to a clinical diagnostic lab setting and is compatible with multiple types of biomarker analyses. We have previously designed a synthetic peptide, known as Vn96 (ME kit), which efficiently isolates EVs from multiple biofluids in a short timeframe without the use of specialized lab equipment. Moreover, it has recently been shown that Vn96 also facilitates the co-isolation of cell-free DNA (cfDNA) along with EVs. Herein we describe an optimized method for Vn96 affinity-based EV and cfDNA isolation from plasma samples and have developed a multiparametric extraction protocol for the sequential isolation of DNA, RNA, and protein from the same plasma EV and cfDNA sample. We are able to isolate sufficient material by the multiparametric extraction protocol for use in downstream analyses, including ddPCR (DNA) and ‘omic profiling by both small RNA sequencing (RNA) and mass spectrometry (protein), from a minimum volume (4 mL) of plasma. This multiparametric extraction protocol should improve the ability to analyse multiple biomarker materials (DNA, RNA and protein) from the same limited starting material, which may improve the sensitivity and specificity of liquid biopsy tests that exploit EV-based and cfDNA biomarkers for disease detection and monitoring.

Liquid Biopsy of Methylation Biomarkers in Cell-Free DNA

2021 ◽  
Author(s):  
Huiyan Luo ◽  
Wei Wei ◽  
Ziyi Ye ◽  
Jiabo Zheng ◽  
Rui-hua Xu
Keyword(s):  
Liquid Biopsy ◽  
Cell Free Dna ◽  
Free Dna
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