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White Papers and Videos

The Importance of Optimizing DNA Extraction Conditions for Formalin Fixed Paraffin Embedded Tissues (FFPET)

White Paper

The pre-analytic extraction of formalin-fixed paraffin-embedded tissues (FFPETs) appears to have a profound effect on the ability to obtain meaningful data from the DNA therein. As part of preparing FFPETs, the formalin fixation step preserves the structure of tissues through covalent modifications but can also damage nucleic acids through that same process. Over the last decade, the emergence of molecular pathology, which benefits from gentler fixation compared to histopathology and, especially, immunohistopathology, has led to changes in how FFPETs are prepared. The remnant FFPETs from over a decade ago may be far from representative of what is now prepared for molecular pathology by many laboratories.

This poster from LGC Clinical Diagnostics discusses the optimization of FFPET extraction for gently fixed samples.

Next-Generation Liquid Biopsy Reference Material Performance Across NGS Assays and Platforms

White Paper

Liquid biopsy testing has grown to support early disease diagnosis, therapy selection, and disease and treatment surveillance in cancer survivors. Recent advances in next-generation sequencing (NGS) have enabled larger panel sizes, allowing the detection of a wider range of pan-cancer genomic alterations. The FDA states assay validation requires testing regions of the genome containing actionable variants with high confidence, but multiplexing at this level across all types of variants is not possible using cancer cell lines or engineered cells.

This poster from LGC Clinical Diagnostics describes the development and multi-site evaluation of the expanded Seraseq ctDNA Mutation Mix v4 reference materials for measuring assay sensitivity and the limit of detection of a range of variant types in cancer liquid biopsy testing.

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

White Paper

Aberrant DNA methylation is associated with many cancers, including breast, liver, bone, and colon, and has been identified as a biomarker for early cancer screening. Liquid biopsies are beginning to screen for DNA methylation in cancer-derived DNA. Epigenetic modifications are being used to assign a tissue of origin to the cancer to direct confirmatory diagnostic procedures. However, accurate assessment of methylation is not trivial, and methods like bisulfite sequencing can result in DNA damage in the sample. Furthermore, obtaining enough cell-free circulating tumor DNA (ctDNA) for assay development, validation, and performance monitoring is a challenge, and reference materials for establishing the analytical validity of measurements of CpG methylation are not widely available.

This poster from LGC Clinical Diagnostics describes new ctDNA-sized reference materials designed to address the challenges associated with assessing the methylation of ctDNA.

Evaluation of Commercially Available Cell-Free DNA Extraction Kits Using Biosynthetic Reference Materials

White Paper

Extraction of cell-free DNA (cfDNA) from a patient’s blood sample is a crucial preanalytical step of the liquid biopsy process. Whether testing is being performed for early disease diagnosis, therapy selection, or disease and treatment surveillance, the input material must be of sufficient quantity and high quality to return informative data. In addition, total capture of the full cfDNA content from a sample is necessary to evaluate variant content present in a cfDNA sample, tumor growth, or recurrence.

This poster from LGC Clinical Diagnostics reports on an evaluation of various commercially available cell-free DNA extraction kits using novel Seraseq ctDNA Extraction Reference Materials developed to optimize laboratory processes and address preanalytical challenges associated with cell-free DNA extraction.

Highly Multiplexed Reference Materials for the Analysis of Copy Number Variations

White Paper

Copy number variations, or CNVs, are DNA segments longer than 1 kb present at a variable copy number in comparison to a reference genome. Ten percent of the human genome contains CNVs, which can be benign or pathogenic. Copy number gain or loss of genes often drives oncogenesis and contributes to the sensitivity and resistance of targeted therapies in cancer patients. Detection and characterization of CNVs are critical for personalized treatment. While next-generation sequencing is a rapidly growing method for CNV detection, rigorous validation and optimization of the bioinformatics algorithms are required to ensure correct CNV calls before clinical application. Multiplexed reference materials for CNV detection will facilitate the validation process of NGS CNV assays, which are currently missing on the market.

This poster from LGC Clinical Diagnostics reports on the development of expanded reference materials to support CNV testing, providing labs with a tool to optimize and challenge their assay’s detection and quantitation of multiple CNVs.

Multi-Site Performance of Highly Multiplexed Next-Generation Liquid Biopsy Reference Material

White Paper

Liquid biopsy testing is rapidly growing, supporting early disease diagnosis, therapy selection in advanced cancers, and disease and treatment surveillance in cancer survivors. Advances in next-generation sequencing (NGS) have enabled larger panel sizes, pan-cancer target sets, and increased sensitivities. To support the expansion of blood-based NGS from small, targeted panels toward comprehensive genome profiling, more precise analytical validation materials are needed to assess assay sensitivity, specificity, and limit-of-detection determination.

This poster from LGC Clinical Diagnostics describes the development and multisite evaluation of expanded Seraseq ctDNA v4 liquid biopsy reference materials.

Improving Genetic Testing for Hereditary Cancers: A Multi-Site Assessment Using a Multiplexed Reference Material

White Paper

Inherited cancers are caused by germline mutations that increase the risk of developing malignancies, such as Lynch syndrome, hereditary breast and ovarian cancer, and many others. As about 5 to 10 percent of cancers are linked to an inherited pathogenic variant, comprehensive genetic testing is important for surveillance and risk-reduction strategies, detecting cancer at earlier stages, and providing tailored treatments and therapies. Inherited cancer assays are developing rapidly, with some panels screening for mutations in hundreds of genes. To validate and assess assay performance, it is usually necessary to source multiple samples with mutations in each gene, which is difficult and costly.

This poster from LGC Clinical Diagnostics describes the development and evaluation of a prototype biosynthetic reference material designed to address these validation challenges for variants relevant in many inherited cancers.

Moving Towards Homologous Recombination Deficiency (HRD) Analysis Standardization: Evaluation of Reference Materials Across Leading HRD Assays

White Paper

Next-generation sequencing assays that measure HRD status are used to stratify ovarian and breast cancer patients and determine eligibility for clinical trials and PARP-inhibitor and platinum-based therapies.

This poster from LGC Clinical Diagnostics reports on the development and evaluation of Seraseq HRD reference materials across various assays that measure genomic instability scores with different methods to enable standardization between HRD assays.

The Importance of Expert Curation in Clinical NGS Testing

White Paper

When a molecular diagnostic lab moves from a 50-gene panel to a 300-gene panel, the number of variants generated in a single test increases dramatically. And, as the range of testing options soars, most molecular diagnostic labs no longer have genetic scientists with expertise in every test indication. Under these conditions, variant interpretation is the bottleneck delaying the uptake of NGS in routine clinical practice and patient management. It falls on the molecular diagnostic labs to do the heavy lifting to filter, prioritize, and gather critical information on detected variants in a matter of days or even hours and summarize the data in a concise report, highlighting clinically relevant information backed up by scientific evidence.

This white paper from Qiagen argues that high-touch, expert curation methods are essential for providing consistent and accurate biological and clinical variant interpretation.

Study Shows Clinical Decision Support Software Exceeds Consistency Among Variant Scientists

White Paper

Numerous clinical decision support systems and knowledgebases have been developed to assist variant scientists and laboratory directors with variant classification. These private and commercially available systems utilize varying degrees of software automation and manually curated literature to provide variant assessment and therapy matching for clinicians. However, significant standardization efforts are required to ensure a consistent level of accuracy and reliability. In contrast to machine curation, human professional expert curation is resource-intensive but can provide consistent and accurate interpretation.

This white paper from Qiagen describes a peer-reviewed study that compared the accuracy and consistency of variant assessments from commercial clinical decision support software to the internal variant interpretation methods of eight laboratories.

Whole Exome and Whole Genome Sequencing in Oncology: Are We There Yet?

White Paper

The utility of whole-genome sequencing to uncover genome-wide structural changes, provide higher-resolution copy number information, and unveil mutations in regulatory regions is recognized in the scientific community. However, despite the continuing reduction in sequencing prices, the cost of large-scale clinical WGS sequencing for cancer remains prohibitive in most places.

This white paper from Qiagen discusses the use of whole-genome sequencing and whole-exome sequencing in cancer testing, covering the technology and knowledge required, the clinical utility, advantages, tradeoffs, costs, and reimbursement considerations.

Panel Analysis: TruSight Oncology 500

White Paper

A single CGP test, can map an individual’s unique genomic profile across all four types of alterations known to drive cancer growth. Capable of interrogating hundreds of genes, CGP provides deeper insight to help oncologists determine the best possible treatment for each patient and chart a treatment journey to identify courses of action should the disease progress.

This sample report from Qiagen shows the results of a TSO 500 panel as interpreted and reported with QCI Interpret, including a summary of the high-level results, individual variant interpretations, AMP/ASCO/CAP classifications, diagnostic and prognostic significance with region-specific clinical trials and approved drugs, and citations for all evidence considered in the report.

The Evolving Role of Diagnostic Labs in Oncology: Navigating Biomarker-Driven Therapies

White Paper

In the past decade, oncology care has witnessed a transformative shift, significantly propelled by the growing field of precision medicine. This transformation has been catalyzed by a deeper understanding of cancer’s underlying biological drivers, unveiling new avenues to combat this multifaceted disease. This rising significance of biomarkers has recalibrated the role of and expectations from diagnostic labs, ushering them into a more proactive and collaborative role in oncology care.

This white paper from Quest Diagnostics delves into the rise of biomarker-driven therapies in oncology, examining how this shift is reshaping the drug and therapy development landscape and exploring the evolving role of diagnostic labs as they transition into active partners in these advancements.

Assess HER2 Status in Solid Tumors to Inform Eligibility for Enhertu

White Paper

Historically, HER2 has been identified as a predictive biomarker only in select tumor types — most notably in breast cancer. However, HER2-positive status is a negative prognostic factor in multiple metastatic solid tumors, often associated with more aggressive disease and a poor prognosis. What if there were more options for patients with HER2-positive (IHC 3+) metastatic solid tumors?

HER2-positive actionability has recently expanded beyond breast and gastric cancers to include non-small cell lung, endometrial, ovarian, cervical, colorectal, pancreatic, biliary tract, and bladder cancers, among others. Performing HER2 IHC testing in metastatic solid tumors at diagnosis can further the understanding of a patient’s disease state and biomarker profile.

This core visual aid from AstraZeneca and Daiichi Sankyo describes the relevance and prevalence of HER2 positivity across metastatic solid tumors; provides detail on the nuances of ASCO-CAP scoring criteria guidelines, including sample requirements and staining interpretation; and outlines who, when, and how to test for HER2 positivity using IHC testing.

The Emergence of Multi-Modal Real-World Data: The Power of Clinico-Genomic Data Versus Traditional RWD Sources

White Paper

The shift toward precision medicine in drug discovery and clinical development underscores the importance of multi-modal real-world data (RWD). Traditional RWD sources often lack detailed biomarker data, crucial for developing targeted therapies for complex diseases. Recent FDA guidelines and advancements in data-linking technologies have enabled the integration of clinical and genomic data, providing a more comprehensive view of patients' health and treatment responses. This integration facilitates more precise clinical trial designs and could significantly improve patient outcomes by enabling the development of personalized therapies. Multi-modal data also allow for population-scale studies and deeper insights into disease mechanisms and treatment efficacy.

This white paper from NeoGenomics explores the potential of clinico-genomic data to revolutionize healthcare by guiding drug development and therapeutic interventions, highlighting the superiority of clinico-genomic data over traditional real-world data sources, which mainly consist of electronic medical records and medical claims.