Tumor mutational burden (TMB) is a promising biomarker for predicting positive patient response to immune checkpoint inhibitors. TMB measurements can be determined using genomic DNA extracted from FFPE-preserved tissue biopsy samples. However, assessment of TMB from a surrogate blood sample (liquid biopsy), referred to as blood TMB (bTMB), is an attractive alternative clinical diagnostic tool that would allow clinicians and patients to avoid the invasive challenge of tissue biopsies.

This poster from LGC SeraCare presents data supporting the use of blood tumor mutational burden (bTMB) reference materials that can aid in the development, validation, and quality control of circulating cell-free DNA assays used to determine TMB scores from blood samples.

Liquid biopsies have begun to incorporate analyses of epigenetic modification for screening purposes to detect cancer-derived DNA in the blood. Additionally, epigenetic modifications are being used to assign a tissue of origin to the cancer to direct confirmatory diagnostic procedures. Obtaining sufficient amounts of ccfDNA for assay development validation, and proficiency testing is difficult. Furthermore, methods of analyzing the epigenetic modifications, such as bisulfite conversion, can damage a significant fraction of the input material; but, failing to carry the methods to completion can result in an over-estimation of methylation.

This poster from LGC SeraCare presents data on three reference materials created to address challenges associated with assessing the methylation of circulating cell-free DNA in order to support the design, optimization, and validation of liquid biopsies for detecting cancer-derived DNA in the blood.

How genomic characteristics indicating homologous recombination deficiency (HRD) are measured, integrated, and distilled varies across assays, which can create uncertainty around treatment options and enrollment into clinical trials. This also makes the path of follow-on companion diagnostics challenging because perfect agreement between imprecise measurements is unlikely.

This poster from LGC SeraCare presents data on the characterization and implementation of a set of reference materials, composed of HRD negative, borderline, and positive tumor/normal matched cell lines, for the standardization of HRD assessment.

Monitoring measurable residual disease (MRD) via liquid biopsy is a method for catching early-stage cancer and disease relapse long before traditional diagnostics, which generally require significant disease progression for detection. Assays in development include those that target patient-specific variants and fixed panels for all patients. Regardless, detection of variant allele frequencies at extremely low levels, well below the limit of detection of typical circulating tumor DNA (ctDNA) assays, presents a challenge that can be surmounted with well-designed reference materials that allow for assessment of sensitivity and specificity.

This poster from LGC SeraCare presents data supporting the use of the Seraseq ctDNA MRD Panel kit, composed of four tumor fractions at decreasing levels, to validate both patient-specific and fixed-panel targeted cfDNA NGS MRD assays.

Lymphoma is a cancer of the lymphatic system and represents the second-largest heme disorder. Next-generation sequencing (NGS) is an important technology to identify the genetic changes involved in lymphoid malignancies. Genome-level understanding of these changes can aid in the identification of lymphoma subtypes and aid in diagnosis, prognosis, therapy selection, and patient risk-stratification.

Cancer biopsies are often preserved by formalin-fixed, paraffin-embedding (FFPE) procedures, which provide long-term preservation but introduce damage to nucleic acids that are present in the tissue, including double-stranded breaks, nicks, and oxidation. The gold standard for Lymphoma diagnosis is the surgical removal of the lymph node, making FFPE the preferred sample format for analysis.

This poster from LGC SeraCare presents data illustrating the performance of biosynthetic reference materials that allow analysis of a broad range of somatic mutations and gene fusions and can aid testing laboratories in accurately detecting and quantifying various types of genetic events in lymphoma patient samples.

Metabolism drives cell behavior, including immune cell activation, differentiation, and effector functions. However, current technologies for the analysis of cellular metabolism lack single-cell resolution and simultaneous characterization of cellular phenotype.

In this white paper, Felix J. Hartmann of Stanford University will describe an approach that characterizes the metabolic regulome of individual cells together with their phenotypic identity. The method, termed single-cell metabolic regulome profiling (scMEP), quantifies proteins that regulate metabolic pathway activity using high-dimensional antibody-based technologies. Dr. Hartmann and colleagues employed single-cell approaches to benchmark scMEP against bulk metabolic assays by reconstructing the metabolic remodeling of in vitro-activated naive and memory CD8+ T cells.

Combining this method with multiplexed ion beam imaging by time of flight (MIBI-TOF), Dr. Hartmann’s team uncovered the spatial organization of metabolic programs in human tissues, which indicated the existence of metabolic niches and exclusion of metabolically repressed immune cells from the tumor–immune boundary.

Dr. Hartmann will discuss how this approach enables robust approximation of metabolic and functional states in individual cells and tissues.

Liquid biopsy has emerged as a novel approach to tumor characterization, offering advantages in sample accessibility and tissue heterogeneity. However, as mutational analysis predominates, the tumor microenvironment has largely remained unacknowledged in liquid biopsy research.

This white paper from Biotech Support Group describes how it may be possible to create a liquid biopsy-based clinical tool to provide relevant information about the state of the tumor microenvironment to accurately quantify intra-tumoral stromal content at numerous time points from a noninvasive blood draw.

This video from Dover Motion describes their collaboration with NanoView Biosciences in which Dover Motion’s motorized microscope stages provided a combined motion solution for X, Y, and Z axes to improve the throughput and reliability of NanoView’s next-generation exosome biomarker imaging platform.

This case study from Dover Motion describes their collaboration with NanoView Biosciences in which Dover Motion’s motorized microscope stages provided a combined motion solution for X, Y, and Z axes to improve the throughput and reliability of NanoView’s next-generation exosome biomarker imaging platform.

This white paper from Biofortuna covers the use and manufacture of lyophilised beads — durable spheres of freeze-dried material formed from accurately measured volumes of customizable formulations — and discusses their utility in point-of-care diagnostics.

Homologous recombination DNA repair deficiency (HRD) creates a permanent genomic scar in cancer cells for many tumor types. Furthermore, HRD is a response biomarker for poly (ADP-ribose) polymerase inhibitors (PARPi) effective therapy. Consequently, HRD measurement has the potential to improve cancer therapy as evidenced by over 100 clinical trials that include HRD today. However, measuring and standardizing HRD quantitation is not straightforward. HRD measurements may include germline and somatic mutation testing, a measure of hypermethylation, and metrics of genomic instability including loss of heterozygosity, telomeric-allelic imbalance, and large-scale genomic rearrangements. This webinar brings together academic, clinical, IVD, and pharmaceutical experts in the clinical genomics and therapeutics fields to discuss the promises and challenges of HRD measurement for disease management. 

Our panelists on this session will be Ravindra Kolhe, M.D., Ph.D., FCAP, Vice-Chairman of Pathology, Associate Dean for Translational Research Medical College of Georgia at Augusta University and Associate Director for Genomics at Georgia Cancer Center, John Jiang, Ph.D., Senior Director of Medical Affairsat Illumina, David Fabrizio Ph.D., Vice President, Translational Strategy at Foundation Medicine, and Yves Konigshofer Ph.D., Director, Technology Development at LGC Clinical Diagnostics.

The low volume of plasma and few genome copies available in liquid biopsy assays limits the detection of variants at low allele frequencies, potentially causing false-negative results. Additionally, the fraction of cell-free DNA varies between cancer types, with circulating tumor DNA sometimes being as low as 0.1 percent of total DNA in a sample. Moreover, clonal hematopoiesis and errors introduced during library preparation can cause false-positive results.

This webinar from LGC Clinical Diagnostics presents data demonstrating the utility of circulating tumor DNA reference materials in supporting the validation and standardization of liquid biopsy assays and in pushing the limit of detection and the sensitivity of such tests.

Tumor mutational burden (TMB) is a promising biomarker for predicting positive patient response to immune checkpoint inhibitors. TMB measurements can be determined using genomic DNA extracted from FFPE-preserved tissue biopsy samples. However, assessment of TMB from a surrogate blood sample (liquid biopsy) referred to as Blood TMB (bTMB), is an attractive alternative clinical diagnostic tool that would allow clinicians and patients to avoid the invasive challenge of tissue biopsies. Obtaining concordant bTMB results across assays has been challenging, thus we have developed the new Seraseq Blood TMB reference materials at various mutational burden levels (7, 13, 20 & 26) from high-quality genomic DNA extracted from tumor-derived and their SNP-matched normal cell lines.

This poster from LGC Clinical Diagnostics demonstrates the use of the Seraseq Blood TMB Score reference materials to provide a tumor-normal matched blood TMB control to aid the development, validation, and quality control of cell-free DNA assays to determine blood tumor mutational burden scores of cancer patients.

Methylation is an important epigenetic modification that influences cellular differentiation and gene expression. Recently, liquid biopsies have started to incorporate analyses of epigenetic modifications for screening purposes to detect cancer-derived DNA in the blood. Additionally, epigenetic modifications are being used to also assign a tissue of origin to the cancer to direct confirmatory diagnostic procedures. However, the robust analysis of methylation is not trivial, nor is establishing the analytical validity of such assays.

This poster from LGC Clinical Diagnostics describes a set of differentially methylated reference materials for analyses of methylation in circulating cell-free DNA (ccfDNA) to enable the development, optimization, and validation of assays that assess the degree of methylation of ccfDNA across the genome and at specific sites.

Monitoring measurable residual disease (MRD) via liquid biopsy is a method for catching early-stage cancer and disease relapse before traditional diagnostics, which generally require significant disease progression for detection. Assays in development include those that target patient-specific variants and fixed panels for all patients. Regardless, detection of variant allele frequencies at extremely low levels, well below the limit of detection of typical circulating tumor DNA (ctDNA) assays, presents a challenge that can be surmounted with well-designed reference materials that allow for assessment of sensitivity and specificity. We developed the Seraseq ctDNA MRD Panel kit composed of four tumor fractions at decreasing levels to meet the validation needs of both patient-specific and fixed panel targeted ccfDNA NGS MRD assays.

This poster from LGC Clinical Diagnostics presents data demonstrating the performance of the Seraseq ctDNA MRD Panel as reference materials for assessing the sensitivity and specificity of patient-specific and fixed-panel liquid biopsy MRD assays.