Expansion of an Academic Molecular Tumor Board to Enhance Access to Biomarker-Driven Trials and Therapies in the Rural Southeastern United States.

Targeting tumor-specific molecular alterations has shown significant clinical benefit. Molecular tumor boards (MTBs) connect cancer patients with personalized treatments and clinical trials. However, rural cancer centers often have limited access to MTB expertise.

Identification of an optimal mutant allele frequency to detect activating , , and mutations in a commercial cell-free DNA next-generation sequencing assay in colorectal and pancreatic adenocarcinomas.

Background: Evaluation for activating mutations in , , and in colorectal cancer (CRC) and in in pancreatic ductal adenocarcinoma (PDAC) is essential for clinical care. Plasma cell-free DNA (cfDNA) next-generation sequencing (NGS) allows convenient assessment of a tumor's molecular profile, however low tumor DNA shedding limits sensitivity. We investigated mutant allele frequency (MAF) of other oncogenic dominant genes to identify a threshold for accurate detection of and mutations in cfDNA.

Concordance Between Genomic Alterations Detected by Tumor and Germline Sequencing: Results from a Tertiary Care Academic Center Molecular Tumor Board.

Objective: The majority of tumor sequencing currently performed on cancer patients does not include a matched normal control, and in cases where germline testing is performed, it is usually run independently of tumor testing. The rates of concordance between variants identified via germline and tumor testing in this context are poorly understood. We compared tumor and germline sequencing results in patients with breast, ovarian, pancreatic, and prostate cancer who were found to harbor alterations in genes associated with homologous recombination deficiency (HRD) and increased hereditary cancer risk.

Mapping SARS-CoV-2 antigenic relationships and serological responses.

During the SARS-CoV-2 pandemic, multiple variants escaping pre-existing immunity emerged, causing concerns about continued protection. Here, we use antigenic cartography to analyze patterns of cross-reactivity among a panel of 21 variants and 15 groups of human sera obtained following primary infection with 10 different variants or after mRNA-1273 or mRNA-1273.351 vaccination.

Automated next-generation profiling of genomic alterations in human cancers.

The lack of validated, distributed comprehensive genomic profiling assays for patients with cancer inhibits access to precision oncology treatment. To address this, we describe elio tissue complete, which has been FDA-cleared for examination of 505 cancer-related genes. Independent analyses of clinically and biologically relevant sequence changes across 170 clinical tumor samples using MSK-IMPACT, FoundationOne, and PCR-based methods reveals a positive percent agreement of >97%.

Implementation of a Molecular Tumor Registry to Support the Adoption of Precision Oncology Within an Academic Medical Center: The Duke University Experience.

Unlabelled: Comprehensive genomic profiling to inform targeted therapy selection is a central part of oncology care. However, the volume and complexity of alterations uncovered through genomic profiling make it difficult for oncologists to choose the most appropriate therapy for their patients. Here, we present a solution to this problem, The Molecular Registry of Tumors (MRT) and our Molecular Tumor Board (MTB).

Next-Generation Sequencing Concordance Analysis of Comprehensive Solid Tumor Profiling between a Centralized Specialty Laboratory and the Decentralized Personal Genome Diagnostics elio Tissue Complete Kitted Solution.

Genomic tumor profiling by next-generation sequencing (NGS) allows for large-scale tumor testing to inform targeted cancer therapies and immunotherapies, and to identify patients for clinical trials. These tests are often underutilized in patients with late-stage solid tumors and are typically performed in centralized specialty laboratories, thereby limiting access to these complex tests. Personal Genome Diagnostics Inc.

Predictive Value of Combining Biomarkers for Clinical Outcomes in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

Introduction: A high tumor mutational burden (TMB) (≥10 mut/Mb) has been associated with improved clinical benefit in non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) and is a tumor agnostic indication for pembrolizumab across tumor types. We explored whether combining TMB with programmed cell death ligand 1 (PD-L1) and pretreatment neutrophil-lymphocyte ratio (NLR) was associated with improved outcomes in ICI-treated NSCLC.

Methods: We retrospectively analyzed patients treated with ICI with Foundation One genomic testing, including TMB.

Donor-Derived Neuroendocrine Carcinoma Transmission to Two Kidney Transplant Recipients Demonstrated by Short Tandem Repeat Analysis: A Case Report.

Cancer transmission from a donor organ to a transplant recipient is a rare but not infrequently fatal event. We report a case of lung cancer transmission from a deceased donor to 2 kidney recipients. Approximately 1 year after uneventful kidney transplantation, both recipients developed acute kidney failure.

Assessment of an Online Tool to Simulate the Effect of Pooled Testing for SARS-CoV-2 Detection in Asymptomatic and Symptomatic Populations.

This diagnostic study describes an online tool created with actual severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus copy number data to help policy makers understand how pooled testing compares with single-sample testing in different populations.

Implementation of a Pooled Surveillance Testing Program for Asymptomatic SARS-CoV-2 Infections on a College Campus - Duke University, Durham, North Carolina, August 2-October 11, 2020.

On university campuses and in similar congregate environments, surveillance testing of asymptomatic persons is a critical strategy (1,2) for preventing transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). All students at Duke University, a private research university in Durham, North Carolina, signed the Duke Compact (3), agreeing to observe mandatory masking, social distancing, and participation in entry and surveillance testing. The university implemented a five-to-one pooled testing program for SARS-CoV-2 using a quantitative, in-house, laboratory-developed, real-time reverse transcription-polymerase chain reaction (RT-PCR) test (4,5).

Early experience with universal preprocedural testing for SARS-CoV-2 in a relatively low-prevalence area.

We implemented universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing of patients undergoing surgical procedures as a means to conserve personal protective equipment (PPE). The rate of asymptomatic coronavirus disease 2019 (COVID-19) was <0.5%, which suggests that early local public health interventions were successful.

Therapeutic outcomes in non-small cell lung cancer with mutations: a single institution, retrospective cohort study.

Background: Data describing therapeutic outcomes in patients with non-small cell lung cancers (NSCLC) with mutations remains limited.

Methods: We conducted a retrospective cohort study of 31 patients with metastatic NSCLC treated at Duke University Hospital who had been identified by next-generation sequencing methods to bear a mutation in their tumor in order to evaluate clinical response to immunotherapy and chemotherapy.

Results: Sixty-five percent of patients identified in this cohort were current or former smokers.

Molecular testing for indeterminate thyroid nodules: Performance of the Afirma gene expression classifier and ThyroSeq panel.

Background: The ThyroSeq mutational panel and Afirma gene expression classifier (GEC) are used to risk stratify cytologically indeterminate thyroid nodules. In the current study, the authors evaluated the performance of these tests within the context of ultrasonographic features and with the incorporation of the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) nomenclature.

Methods: The authors reviewed nodules using ThyroSeq or Afirma GEC testing.

Young Investigator Challenge: Molecular testing in noninvasive follicular thyroid neoplasm with papillary-like nuclear features.

Background: Molecular testing provides an important ancillary study for thyroid nodules with indeterminate cytology. The nomenclature shift to "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) will impact the performance of molecular tests. For the current study, the authors reviewed the performance of the Afirma gene-expression classifier (GEC) and the University of Pittsburgh Medical Center (UPMC) targeted mutation panel tests in thyroid nodules that were subsequently diagnosed as NIFTP on surgical resection.

False positives in multiplex PCR-based next-generation sequencing have unique signatures.

Next-generation sequencing shows great promise by allowing rapid mutational analysis of multiple genes in human cancers. Recently, we implemented the multiplex PCR-based Ion AmpliSeq Cancer Hotspot Panel (>200 amplicons in 50 genes) to evaluate EGFR, KRAS, and BRAF in lung and colorectal adenocarcinomas. In 10% of samples, automated analysis identified a novel G873R substitution mutation in EGFR.

Molecular testing for the BRCA1 and BRCA2 Ashkenazi Jewish founder mutations: a report on the College of American Pathologists proficiency testing surveys.

Purpose: The purpose of this study was to analyze laboratory performance on proficiency testing surveys offered jointly by the College of American Pathologists/American College of Medical Genetics and Genomics biannually for the three common Ashkenazi Jewish founder mutations in the BRCA1 and BRCA2 genes.

Methods: Survey responses were analyzed for accuracy of genotype determination and the associated clinical interpretation. Data on an individual laboratory's participation over time, number of samples tested, turnaround time, and test methodology were also reviewed.

Genes with bimodal expression are robust diagnostic targets that define distinct subtypes of epithelial ovarian cancer with different overall survival.

In some cancer types, certain genes behave as molecular switches, with on and off expression states. These genes tend to define tumor subtypes associated with different treatments and different patient survival. We hypothesized that clinically relevant molecular switch genes exist in epithelial ovarian cancer.

Type III TGF-β receptor enhances colon cancer cell migration and anchorage-independent growth.

The type III TGF-β receptor (TβRIII or betagylcan) is a TGF-β superfamily coreceptor with emerging roles in regulating TGF-β superfamily signaling and cancer progression. Alterations in TGF-β superfamily signaling are common in colon cancer; however, the role of TβRIII has not been examined. Although TβRIII expression is frequently lost at the message and protein level in human cancers and suppresses cancer progression in these contexts, here we demonstrate that, in colon cancer, TβRIII messenger RNA expression is not significantly altered and TβRIII expression is more frequently increased at the protein level, suggesting a distinct role for TβRIII in colon cancer.

Donor cell leukemia in umbilical cord blood transplant patients: a case study and literature review highlighting the importance of molecular engraftment analysis.

Donor cell neoplasms are rare complications of treatment regimens that involve stem cell transplantation for hematological malignancies, myelodysplastic processes, or certain genetic or metabolic disorders. We report a case of donor cell leukemia in a pediatric patient with a history of acute myeloid leukemia that manifested as recurrent AML FAB type M5 fourteen months after umbilical cord blood transplantation. Although there was some immunophenotypic drift from the patient's original AML and their posttransplant presentation, the initial pathological impression was of recurrent disease.

SMAD4 is required for development of maximal endotoxin tolerance.

Initial exposure of monocytes/macrophages to LPS induces hyporesponsiveness to a second challenge with LPS, a phenomenon termed LPS tolerance. Molecular mechanisms responsible for endotoxin tolerance are not well defined. We and others have shown that IL-1R-associated kinase (IRAK)-M and SHIP-1 proteins, negative regulators of TLR4 signaling, increase in tolerized cells.

Intratumor heterogeneity and precision of microarray-based predictors of breast cancer biology and clinical outcome.

Purpose: Identifying sources of variation in expression microarray data and the effect of variance in gene expression measurements on complex predictive and diagnostic models is essential when translating microarray-based experimental approaches into clinical assays. The technical reproducibility of microarray platforms is well established. Here, we investigate the additional impact of intratumor heterogeneity, a largely unstudied component of variance, on the performance of several microarray-based assays in breast cancer.