Accurate detection of EBV in tumors is essential for refining diagnosis and guiding management of EBV-associated cancers. This validation study evaluated the performance of the FoundationOne CDx (F1CDx) and FoundationOne Heme (F1H) next-generation sequencing (NGS) assays for detecting EBV compared to the reference standard EBV-encoded RNA (EBER) in situ hybridization (ISH). A total of 413 samples of gastric carcinoma, squamous cell carcinoma (predominantly nasopharyngeal carcinoma), and diffu...

Diagnostic analysis of messenger RNA is essential as altered splicing is a frequent cause of genetic diseases. High throughput splicing studies remain difficult to implement in routine diagnostics. This is why we developed SEALigHTS (splice and expression analyses by ligation and high throughput sequencing), a cost-effective and easy-to-implement technique designed for simultaneous analysis of RNA from multiple patients on a panel of genes, using probes designed at exon extremities. Following...

Genomic testing has proven utility in disease diagnostics, guiding clinical management and improving outcomes. Use of high throughput sequencing by clinical laboratories has generated opportunities and challenges in data analysis resulting in the emergence of a laboratory role termed Variant Scientist. The aim of this study was to characterize this laboratory role. We developed a thirty-item survey to collect information describing the current demographic landscape, salary ranges, work enviro...

Genomic profiling of cancers informs diagnostic and prognostic classification and aids in selection of targeted therapeutics. Targeted, next-generation sequencing of cancer-specific genes is clinically feasible and enables comprehensive somatic reporting; without a matched germline specimen, germline alterations can confound analyses of the somatic profile and create uncertainty in interpretation. We report the validation and implementation of optional matched tumor/germline sequencing in our...

Cancer treatment costs pose a significant global economic burden. By facilitating treatment plans tailored to the genomic profile of patients’ cancer, genomic testing has the potential to reduce healthcare costs. Using real-world evidence, this study compared the cost-effectiveness of comprehensive genomic profiling (CGP) versus small panel (SP) testing in patients with advanced non-small cell lung cancer (aNSCLC) in the US and Germany. A partitioned survival model was developed to estimate t...

Asian-type DEL (RHD, c.1227G>A) is relatively prevalent in East Asians and is essential to detect in serologic rhesus (Rh) D-negative individuals. Despite the recognized importance of identifying Asian-type DEL, traditional detection methods, such as adsorption-elution and Sanger sequencing, are complex and time-consuming. A reliable method is required for the rapid and precise detection of Asian-type DEL. A novel multiplex real-time PCR assay using allele-specific TaqMan hydrolysis probes wa...

Molecular syndromic assays have improved respiratory diagnostics by enabling the simultaneous detection of multiple pathogens from a single sample. However, fixed-panel designs may not align with age-specific prevalence patterns or evolving epidemiologic trends, limiting clinical utility and reimbursement viability. In this study, 1520 positive nasopharyngeal swabs from symptomatic individuals collected during the 2022 to 2023 respiratory season were analyzed by using the LIAISON PLEX Respira...

Blood collection, plasma processing, and cell-free DNA (cfDNA) purification were optimized to capture circulating tumor DNA without blood cell background DNA among 874 patients with cancer. cfDNA comprised predominantly mononucleosomal fragments (n = 874; x¯ ± SD = 166 ± 5 bp) that generated comparably sized sequencing reads (x¯ ± SD = 162 ± 25 bp). Despite a vast range of cfDNA concentrations (0.50 to 1132.9 ng/mL) across 21 tumor types, matched tumor and blood specimens (n = 430 patients) r...

Genetic testing, as part of the medico-legal autopsy in cases of suspected sudden cardiac death, has been recommended for several years, however, are rarely performed. The aim was to assess the value of postmortem genetic testing in unexplained sudden death in the young. This is a prospective study including all cases with unexplained natural sudden death cases in individuals ≤50 years old undergoing a legal autopsy. Postmortem genetic testing was routinely performed in cases under 35 and aft...

Accurate genomic characterization of respiratory syncytial virus (RSV) is crucial for studies of epidemiology and viral evolution, including monitoring potential escape from newly authorized vaccines and prophylactic monoclonal antibodies. We adapted a viral genome tiling amplicon panel (UW-ARTIC) and developed a custom bioinformatic pipeline for high-throughput, cost-effective sequencing of both RSV-A and RSV-B subgroups. We established genome acceptability criteria and determined the perfor...

myeloMATCH is a National Cancer Institute (NCI) precision medicine clinical trial initiative to evaluate treatments for acute myeloid leukemia and myelodysplastic syndrome based on a leukemia’s diagno...

Human papillomavirus (HPV) is linked to various cancers, including cervical, anal, and head and neck cancers. Conventional methods for HPV genotyping and commercial platforms are limited to detecting high-risk HPV genotypes primarily in gynecologic samples. Because of changing trends in the epidemiology and pathogenesis, there is a growing need for HPV genotyping techniques applicable to emerging clinical contexts involving diverse sample types, such as head and neck or anal samples, particul...

It was recently reported that follicular lymphoma (FL) with BCL6 rearrangement (R) is associated with favorable progression-free survival, whereas BCL2-R and BCL2-6-R cases are associated with disease progression. However, the pathologic mechanism remained unexplored. This study analyzed the mutational landscape and immune microenvironment of 31 FL cases, including 16 BCL2-R, 11 BCL6-R, and 4 BCL2-6-R FL cases. The method included an in-house next-generation targeted sequencing panel of 168 g...

Tissue availability is often a limiting factor in obtaining comprehensive genomic profiling to identify actionable oncogenic drivers in tumors from patients with cancer. The utility of performing comp...

With the evolution of next-generation sequencing–based testing in molecular diagnostics laboratories, the clinical role of bioinformaticians has also evolved. The Association for Molecular Pathology's Clinical Bioinformatician Body of Knowledge aims to define the various roles the clinical bioinformatician operates individually or within a clinical bioinformatics team, along with proficiencies and skill sets that may be required or desirable across these roles. One of the most common professi...

Copy number variants (CNVs), structural alterations in the genome involving duplication or deletion of DNA segments, are implicated in various health conditions. Despite their clinical significance, a...

Chromosomal structural variants (SVs) are major contributors to cancer development. Although multiple methods exist for detecting SVs, they are limited in throughput, such as fluorescent in situ hybri...

Bile duct brushings are noninvasive samplings of cells from the biliary tract for cytologic evaluation and are useful to diagnose pancreaticobiliary malignancies. Although specificity of cytology is s...

Preimplantation genetic testing (PGT) is an essential tool for selecting embryos free of genetic abnormalities. However, current PGT methods often require separate platforms for aneuploidy (PGT-A), mo...