We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us

Download Mobile App




CSF Liquid Biopsy Sequencing Tracks Glioma Evolution

By LabMedica International staff writers
Posted on 06 Feb 2019
Genetic tumor profiling of gliomas is used to classify disease and guide therapy, but involves brain surgery for tissue collection; repeated tumor biopsies may be necessary for accurate genotyping over the course of the disease.

While the detection of circulating tumor DNA (ctDNA) in the blood of patients with primary brain tumors remains challenging, sequencing of ctDNA from the cerebrospinal fluid (CSF) may provide an alternative way to genotype gliomas with lower morbidity and cost.

A large team of scientists led by the Memorial Sloan Kettering Cancer Center (New York, NY, USA) tracked traces of gliomas in CSF by collecting samples from 85 glioma patients who previously received a lumbar puncture because they showed neurological signs or symptoms of brain tumors. More...
Patient diagnoses included 13 grade II gliomas, 26 grade II gliomas, and 54 grade IV gliomas. All patients had received treatment for glioma before CSF collection, including surgery, radiation, and at least one systemic tumor-directed chemotherapy.

After extracting 3 mL of CSF from each patient through a spinal tap, the team ran the sample on a centrifuge to separate the pellets from supernatant, which contained ctDNA. While normal CSF typically contains a low white blood cell count, the team noted that including pellets dilutes the tumor signature in a sample. The investigators used MSKCC's MSK-IMPACT next-generation sequencing assay to analyze samples for genes relevant to glioma. Afterward, the team ran the results through a bioinformatics analysis pipeline, which included a mutation-calling element that MSKCC developed with the MSK-IMPACT.

The scientists detected tumor-derived DNA in CSF from 42 out of 85 patients and found that the genetic material was linked to disease burden and adverse outcome. They also examined whether combinations of genetic alterations, lower-grade glioma signatures, that they detected in the CSF could be matched to the signature of the original tumor. Sequencing all available tumor biopsies from 36 patients who had positive CSF ctDNA, they found that CSF and tumor samples shared mutations in all 20 patients with wild type glioblastomas (GBMs) that were not hypermutated. The most common alterations in the samples included mutations in the TERT promoter, the protein coding regions of TP53, IDH1, deletions of CDKn2A and CDKN2B, amplifications of EGFR, and EGFR-variant III deletion.

Alterations that occur early during tumorigenesis, such as co-deletion of chromosome arms 1p and 19q (1p/19q codeletion) and mutations in the metabolic genes isocitrate dehydrogenase 1 (IDH1) or IDH2, were shared in all matched ctDNA-positive CSF–tumor pairs, whereas growth factor receptor signaling pathways showed considerable evolution. Michael Berger, PhD, a co-author of the study, said, “Compared to other liquid biopsy applications, cerebrospinal fluid has the potential to enable more sensitive detection of ctDNA because most of the cell-free DNA in CSF is shed from tumor cells. There is very little background DNA from non-cancerous cells, in contrast to plasma where often only a tiny fraction of the cell-free DNA is actually derived from tumor cells.” The study was published on January 23, 2019, in the journal Nature Research.

Related Links:
Memorial Sloan Kettering Cancer Center


Gold Member
Quality Control Material
iPLEX Pro Exome QC Panel
Collection and Transport System
PurSafe Plus®
New
Silver Member
PCR Plates
Diamond Shell PCR Plates
Capillary Blood Collection Tube
IMPROMINI M3
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








Channels

Hematology

view channel
Image: New evidence shows viscoelastic testing can improve assessment of blood clotting during postpartum hemorrhage (Photo courtesy of 123RF)

Viscoelastic Testing Could Improve Treatment of Maternal Hemorrhage

Postpartum hemorrhage, severe bleeding after childbirth, remains one of the leading causes of maternal mortality worldwide, yet many of these deaths are preventable. Standard care can be hindered by delays... Read more

Immunology

view channel
Image: The CloneSeq-SV approach can allow researchers to study how cells within high-grade serous ovarian cancer change over time (Photo courtesy of MSK)

Blood Test Tracks Treatment Resistance in High-Grade Serous Ovarian Cancer

High-grade serous ovarian cancer (HGSOC) is often diagnosed at an advanced stage because it spreads microscopically throughout the abdomen, and although initial surgery and chemotherapy can work, most... Read more

Pathology

view channel
Image: The new system allows surgeons to identify genotyping of brain tumors and determine optimal resection margins during surgery (Photo courtesy of Nagoya University)

New Technique Detects Genetic Mutations in Brain Tumors During Surgery within 25 Minutes

Determining the genetic profile of brain tumors during surgery is crucial for improving patient outcomes, but conventional analysis methods can take up to two days, delaying critical decisions.... Read more

Industry

view channel
Image: The enhanced collaboration builds upon the successful launch of the AmplideX Nanopore Carrier Plus Kit in March 2025 (Photo courtesy of Bio-Techne)

Bio-Techne and Oxford Nanopore to Accelerate Development of Genetics Portfolio

Bio-Techne Corporation (Minneapolis, MN, USA) has expanded its agreement with Oxford Nanopore Technologies (Oxford, UK) to broaden Bio-Techne's ability to develop a portfolio of genetic products on Oxford... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.