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White Papers and Videos

Development of Patient-Derived Sex Chromosome Aneuploidy Reference Materials for NIPT

White Paper

Sex chromosome aneuploidies (SCAs) are genetic conditions caused by abnormalities in the number of X and Y sex chromosomes, which include 45, X (Turner syndrome), 47, XXY (Klinefelter syndrome), and 47, XYY (Jacobs syndrome). With a combined incidence of ~1 in 400 live births, SCAs occur more frequently than trisomy 21 (1:700). The majority of commercially available cell-free DNA (cfDNA) screens, also known as non-invasive prenatal tests (NIPT), can provide optional sex aneuploidy analysis.

Guidelines recommend the use of external run controls to validate test performance for SCAs when NIPTs are first implemented in a clinical lab and for routine performance monitoring. However, this can be problematic due to the rarity, low volume, and ethical considerations in obtaining clinical samples. This is especially important as current NIPT technologies have a lower sensitivity and positive predictive value for SCAs as compared to trisomy 21.

This poster from LGC SeraCare presents the development, characterization, and clinical performance of novel SNP-matched sex chromosome aneuploidy reference materials on several commercial NIPT assays.

Respiratory Tract Infections: Why Accurate Detection and Identification of Pathogens is at the Core of Infection Treatment

White Paper

This infographic from Thermo Fisher Scientific summarizes pathogens, symptoms, and testing methods for respiratory tract infections and describes the benefits of molecular testing.

How Digital Pathology Ensures Ongoing Diagnosis in a Time of Crisis

White Paper

This white paper from Tribun Health discusses how digital pathology helped to address challenges within pathology departments precipitated by the COVID-19 pandemic at three hospitals and how they ensured continuity of cancer diagnosis during lockdowns and staff outages.

Four Good Reasons to Switch to Digital Pathology

White Paper

This white paper from Tribun Health discusses the considerations and benefits of transitioning from histopathological diagnosis with a microscope to virtual microscopy using a computer, including meeting the requirements of precision medicine, streamlining workflows, improving flexibility, and enhancing the security and traceability of diagnosis.

Digital Pathology at Paris Saclay Hospital Group: Process, Benefits, and Recommendations

White Paper

This white paper from Tribun Health discusses the experience of integrating digital pathology for routine diagnosis in Paris Saclay Hospital’s pathology department, highlighting the transition to digital pathology, current progress, benefits to pathologist workflow, and future projects in the department.

Concordance Between Digital PCR and Next-Generation Sequencing in Measuring Allele Frequency for Genomic Reference Materials

White Paper

Genomic reference material (RM) for next-generation sequencing (NGS) has been widely utilized in clinical diagnosis, NGS product development, and patient selection for clinical trials or treatments. To better serve these purposes, RM is expected to have precise allele frequencies (AFs) for all variants contained within. Several methods have been used to quantify AFs during RM development, including droplet digital PCR (dPCR) and NGS. At LGC Clinical Diagnostics, dPCR has been chosen to quantify and finalize the AFs in our genomic RMs because of its proven sensitivity, ease of use, accuracy, and low cost. Customers report consistent satisfaction with the RMs and associated AFs claimed, but as yet, data directly comparing the two technologies are limited.

This white paper from LGC SeraCare describes a study that analyzed data from two different types of genomic reference materials and demonstrates that next-generation sequencing shows a high level of concordance to variant calls generated with droplet digital PCR as the precise allele frequency-defining method.

How Co-Occurring Oncogenic Mutations Impact Clinical Outcomes

White Paper

Next-generation sequencing (NGS) has revealed comprehensive genomic tumor profiles and showed that the presence of a single somatic mutation can be insufficient to implicate a gene in the development of cancer. While initial studies of somatic mutations focused on the impact of single mutations, researchers are now investigating the cooperative effects induced by multiple mutations arising simultaneously in one tumor. The event of multiple mutations emerging concurrently is referred to as co-mutation or mutation co-occurrence. Co-mutations have been investigated in many tumor types, and studies have suggested that co-mutations might be a core determinant of oncogene-driven cancers.

This white paper from Qiagen presents use cases in acute myeloid leukemia and glioma demonstrating the importance of adequately annotating and interpreting co-mutations in human cancers, and how the presence of co-occurring mutations can inform diagnosis, prognosis, and therapy options.

Development of Blood TMB Reference Materials for Validation of cfDNA-Based Targeted NGS Assays That Measure TMB in Patient Blood Samples

White Paper

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.

Novel Reference Materials for the Analysis of Methylation in Liquid Biopsies

White Paper

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.

The Challenge of Standardizing the Measurement of an Imprecise Biomarker like HRD

White Paper

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.

Reference Materials for ctDNA-Based Measurable Residual Disease (MRD) Assay Development and Validation

White Paper

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.

Comprehensive NGS-Based Reference Materials for Variant Detection in Lymphoid Cancer

White Paper

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.

Development of Blood TMB Reference Materials for Validation Of ccfDNA-Based Targeted NGS Assays That Measure Tumor Mutational Burden in Patient Blood Samples

White Paper

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.

Reference Materials for the Analysis of Methylation in Circulating Cell-Free DNA

White Paper

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.

Development and Performance of ctDNA-Based Measurable Residual Disease (MRD) Reference Materials

White Paper

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.