Diagnostic Precision

A SeraCare blog focused on precision medicine and advanced clinical diagnostics

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How to resolve the challenges of MRD?

Category: NGS, ctDNA, cfDNA, reference materials, MRD

Posted by Yves Konigshofer, PhD on Oct 7, 2020
  This is part 2 of 2 of the MRD blog post. (Click here for part 1). In this section, we will discuss how to overcome some of the most common challenges of MRD testing. Overcoming the Challenges In order to mitigate sequencing errors, methods using Molecular Barcodes (MBCs), Unique Molecular Identifiers (UMIs), etc. (which are essentially all the same) may be used, where each starting molecule is sequenced many times. The MBCs are then used to generate consensus sequences from sequences that were likely obtained from the same starting molecule. The assumption is that errors appear due to somewhat stochastic processes and that the consensus sequences will likely be correct. This requires many observations of the same starting molecule, so it will be recommended to generate 10-fold more sequences than there are molecules. Therefore, with 8,000 genomic equivalents, we might want to target a sequencing depth of 80,000. This is a reason why using 10-fold more input ccfDNA may not necessarily be a good thing (in addition to having to obtain a 10-fold larger liquid biopsy) since we may have to increase sequencing depth accordingly to 800,000, which could increase the cost of sequencing 10-fold, which could reduce the likelihood for payment and running the assay profitably.
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So, you want to monitor Measurable Residual Disease? What are the challenges?

Category: NGS, ctDNA, cfDNA, reference materials, MRD, Minimal Residual Disease

Posted by Yves Konigshofer, PhD on Oct 1, 2020
Part 1 of 2   Background Measurable Residual Disease (MRD) monitoring – for purposes of this blog – will be the act of looking for somatic variants in a liquid biopsy sample by analyzing circulating cell-free DNA (ccfDNA). This is done to monitor the disappearance of a metastatic solid tumor during treatment and to follow any future reemergence of that cancer. Analyzing ccfDNA assumes that circulating tumor DNA (ctDNA) will be present, and the median ctDNA frequency in patient samples across cancers seems to be around 0.5 to 1 %. Thus, the median variant allele frequencies (VAFs) of the somatic variants will start around this range, and the goal of MRD monitoring is to be able to detect them at much lower VAFs. This can be challenging and if we are going to design an assay for MRD monitoring, then we need to be aware of them and overcome them.
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So Many Posters, So Little Time

Category: ctDNA, AACR, RNA fusion, TMB

Posted by Sam Blier on Jun 6, 2019
Cancer research is purposely methodical and measured. So – somewhat paradoxically – it can be difficult to keep up with the steady stream of discoveries in the literature and presented at conferences like AACR. As a developer and manufacturer of platform-agnostic NGS reference standards, we’re in a unique position to collaborate with cancer genomics assay developers, laboratories, pharmaceutical companies, and other organizations invested in more precise and robust cancer tests.
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Newly Published Multi-Laboratory Study Provides Utility and Validation of the Use of ctDNA Reference Standards

Category: ctDNA, cfDNA

Posted by Russell Garlick, PhD on May 30, 2019
I am pleased to share findings from a newly published peer-reviewed study with foundational circulating tumor DNA (ctDNA) pre-analytical and analytical testing in multiple technologies and assay chemistries. The study, “Multi-laboratory Assessment of a New Reference Material for Quality Assurance of Cell-Free Tumor DNA Measurements,” was just published in The Journal of Molecular Diagnostics (He, Stein et al. 2019).
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Customer Data: Use of Seraseq ctDNA Reference Samples to Validate Detection of Low Frequency Variants in a cfDNA-based NGS Lung Cancer Panel

Category: ctDNA, SeraSeq, AMP, cfDNA, Lung Cancer

Posted by Omo Clement, PhD on Feb 14, 2019
At the recently-concluded 2018 AMP Meeting, researchers at the New York Presbyterian Hospital (NYPH) and Weill Cornell Medical Center (WCMC) presented a poster1 on the validation of an Oncomine™ cell-free DNA Lung Assay using ctDNA NGS standards developed by SeraCare (Seraseq® ctDNA v2 Reference Materials),2
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Keys to Better Liquid Biopsy Assay Sensitivity – AMP Corporate Workshop Video

Category: NGS, ctDNA, AMP, liquid biopsy

Posted by Sam Blier on Jan 24, 2019
“So as everyone here is aware, I’m sure, detection of circulating tumor DNA is challenging. There’s very little of it, to start with.” Hardly a revolutionary statement by Tony Godfrey, PhD, (Associate Chair, Surgical Research and Associate Professor of Surgery, Boston University School of Medicine) but an important acknowledgement from a leading expert of the difficulty faced by laboratorians
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Tips for Better EGFR Mutation Testing

Category: ctDNA, SeraSeq, EGFR

Posted by Catherine Huang, PhD on Jan 10, 2019
Tips for Better EGFR Mutation Testing Molecular testing of genomic alterations in the EGFR gene is critical to personalized treatment decisions for patients with advanced non-small cell lung cancer (NSCLC). However, the testing landscape is complex. Some mutations confer sensitivity, and others confer resistance to anti-EGFR targeted therapies.
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Two Must-See Liquid Biopsy Poster Videos From AMP 2018

Category: ctDNA, SeraSeq, AMP, liquid biopsy, cfDNA

Posted by Sam Blier on Dec 7, 2018
  Of the many fantastic posters presented at AMP’s Annual Meeting in San Antonio, two concerning NGS-based liquid biopsy assays stood out. Both presenters described how their organizations are working to reliably detect pathogenic variants at extremely low allele frequencies – efforts critical to the clinical adoption of NGS-based liquid biopsy assays.
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How A New Generation of ctDNA Reference Standards Are Enabling the Promise of Precision Medicine

Category: cancer, NGS, ctDNA, SeraSeq, liquid biopsy

Posted by Omo Clement, PhD on Jun 14, 2018
An important goal in cancer disease management is early detection. When detected early, disease progression can be significantly mitigated with a plethora of options (targeted therapy, chemotherapy, surgery, etc.) available to medical practitioners, to afford progression free survival and a higher quality of life. A great promise of liquid biopsies is the possibility of early detection of cancer long before clear evidence of lesions and tumor growth observable by imaging or other techniques.1 As proxy for solid tissue biopsies, plasma-based liquid biopsy application is rapidly gaining traction in cancer disease diagnosis, progression, monitoring, and in predicting resistance to treatment options.2
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Sensitive ctDNA Assays are Required for Minimal Residual Cancer Detection

Category: ctDNA, SeraSeq

Posted by Russell Garlick, PhD on May 29, 2018
The 11th International Symposium on Minimal Residual Cancer was held this month and much of the conference was devoted to new minimally invasive methods for circulating tumor cell enrichment and or the analysis of circulating tumor DNA. Today’s clinical needs are to measure disease burden, track mutations over time, or to detect early resistance and all of these applications require extremely sensitive, robust assays.
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