Advances in Molecular Pathology, 2020

1st Edition, Volume 3-1 - November 7, 2020
Editor: Gregory J. Tsongalis
Language: English
Hardback ISBN:
9 7 8 - 0 - 3 2 3 - 7 2 2 2 6 - 1
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 7 2 2 2 7 - 8

This issue of Advances in Molecular Pathology will provide a comprehensive review of the most current practices, trends, and developments in the field of Molecular Pathology.… Read more

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This issue of Advances in Molecular Pathology will provide a comprehensive review of the most current practices, trends, and developments in the field of Molecular Pathology. Publishing on an annual basis, the volume will be divided into 7 sections: Genetics, Hematopathology, Infectious Disease, Pharmacogenomics, Informatics, Solid tumors, and Identity/HLA. Led by Dr. Gregory Tsongalis of Dartmouth University, a team of experienced pathologists from institutions across the country oversee annual topic and expert author selection.

Cover image
Title page
Table of Contents
Copyright
Editorial Board
Contributors
Preface
The SARS-CoV-2 Pandemic
The 2020 Wild, Wild West of Diagnostics
Key points
Maintaining Laboratory Services in a Rural Academic Medical Center During the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic: What Worked and What Did Not (February 29–May 1, 2020)
Key points
Introduction
Preparations and timelines for the Dartmouth-Hitchcock response to the severe acute respiratory syndrome coronavirus 2 pandemic
What worked
What did not work
Summary
Laboratory Testing of Severe Acute Respiratory Virus Coronavirus 2: A New York Institutional Experience
Key points
Introduction
Laboratory tests for detection of severe acute respiratory virus coronavirus 2
Rapid point-of-care molecular assays
Serologic assays for coronavirus disease 19
Genetics
Precision Therapies in Neurodevelopmental Disorders: Update on Gene Therapies
Key points
Introduction
Targeted gene therapy drugs in neurodevelopmental disorders
Risks and challenges of gene therapy
Future of neurodevelopmental disorders genetic therapies
EpiSigns: DNA Methylation Signatures in Mendelian Neurodevelopmental Disorders as a Diagnostic Link Between a Genotype and Phenotype
Key points
Introduction
Episignatures as diagnostic biomarkers in neurodevelopmental disorders
Episignatures as phenotypic biomarkers in neurodevelopmental disorders
Challenges in DNA methylation episignature analysis
Hematopathology
Molecular Pathways and Potential for Targeted Therapies in the Treatment of Early T-cell Precursor Acute Lymphoblastic Leukemia
Key points
Introduction
Significance
Present relevance and future avenues to consider or to investigate
Summary
Molecular Genomic Advances in Chronic Myelomonocytic Leukemia
Key points
Introduction
Morphologic findings in chronic myelomonocytic leukemia
Cytogenetic abnormalities in chronic myelomonocytic leukemia
Mutations in chronic myelomonocytic leukemia
Approach to diagnosis and work-up
Summary
Erdheim-Chester Disease: A Review of Molecular Genetic and Clinical Features
Key points
Introduction
Summary of clinical-pathologic features
The genomic landscape in Erdheim-Chester disease
The mitogen-activated protein kinase/extracellular signal-regulated kinase pathway
Mitogen-activated protein kinase, protein kinase B/mammalian target of rapamycin, and other pathway interactions
Molecular diagnostics in the evaluation of Erdheim-Chester disease
Erdheim-Chester disease molecular pathology as a guide for targeted therapy
Molecular pathology and Erdheim-Chester disease/Langerhans cell histiocytosis disease ontogeny
Summary
Utility of Fluorescence In Situ Hybridization in Clinical and Research Applications
Key points
Introduction
Significance
Clinical use of fluorescence in situ hybridization and its major areas of advancement
Digitizing and automating fluorescence in situ hybridization imaging
Considerations for fluorescence in situ hybridization DNA probe validation
Role of in situ hybridization assays in hematological malignancies with a chromosomal basis
Fluorescence in situ hybridization probe design strategies to assess chromosomal correlates in acute myeloid leukemia
Fluorescence in situ hybridization probe strategies for detecting myeloproliferative neoplasms
Fluorescence in situ hybridization probe strategies detecting chromosomal correlates in mature B-cell neoplasms
Role of single nucleotide polymorphism chromosomal microarrays in hematological malignancies
Expanding traditional applications of fluorescence in situ hybridization
Future considerations
Summary
Germline Mutations with Predisposition to Myeloid Neoplasms
Key points
Introduction
Myeloid neoplasms with germline predisposition and preexisting platelet disorders
Myeloid neoplasms with germline predisposition without a preexisting disorder or organ dysfunction
Myeloid neoplasms with germline predisposition and other organ dysfunction
Rationale for universal genetic testing for germline predisposition to acute myeloid leukemias/myelodysplastic syndrome
Significance of the knowledge of germline predisposition to myeloid neoplasms in diagnosis and management
Infectious Disease
The Role of Human Immunodeficiency Virus Molecular Diagnostics in Ending the Epidemic
Key points
Molecular diagnostics to end the human immunodeficiency epidemic
The role of molecular diagnostics in primary prevention
The role of molecular diagnostics in secondary prevention
Pharmacogenomics
Pharmacogenomics of Drug-Induced Liver Injury
Key points
Introduction
Historical perspective
HLA genotype as a risk factor for drug-induced liver injury
Non-HLA immunogenetic risk factors
Mechanism for immunogenetic associations in drug-induced liver injury
Drug disposition genotypes as risk factors
Present relevance and future avenues to consider or to investigate
Summary
Bringing Pharmacogenetics to Prescribers: Progress and Challenges
Key points
Introduction
Navigating an expanding evidentiary landscape
Continuous and effective use of pharmacogenetic test results relies on systems and experts
Infrastructure for delivering pharmacogenetic insight
Regulatory framework
Summary and future directions
Precision Medicine Using Pharmacogenomic Panel-Testing: Current Status and Future Perspectives
Key points
Introduction
The lack of evidence of (cost-) effectiveness supporting a pharmacogenomics-panel approach
Finding the optimal target population and timing for delivering pharmacogenomics
The lack of tools supporting implementation of pharmacogenomics-panel testing
Future perspectives
Summary
Informatics
Artificial Intelligence in the Genetic Diagnosis of Rare Disease
Key points
Introduction
Significance
Discussion/summary
Building Infrastructure and Workflows for Clinical Bioinformatics Pipelines
Key points
Introduction
Significance
Computational infrastructure for bioinformatics
On-premise computing infrastructure
Cloud-based service providers
Data storage
Data transfer
Container technology
Bioinformatics pipeline design and implementation frameworks
Principles for robust pipeline implementation
Native/basic pipeline frameworks
Modern workflow management frameworks
Domain specific language systems: Nextflow and Snakemake
Commercial platforms: DNANexus and SevenBridges
Tertiary analysis systems
Interoperability and data integration with clinical informatics
Discussion
Solid Tumors
Microsatellite Instability Testing and Therapy Implications
Key points
Introduction
Clinical biology of DNA mismatch repair deficiency and microsatellite instability
Testing for Mismatch Repair Deficiency and Microsatellite Instability
Present relevance and future avenues of investigation
Identity/HLA
HLA Typing by Next-Generation Sequencing: Lessons Learned and Future Applications
Key points
Introduction
HLA typing in the beginning
Molecular-based HLA typing era
Next-generation sequencing–based HLA typing
Future for clinical next-generation sequencing HLA typing
HLA and Autoimmune Disease
Key points
Introduction
The genetic component
The basic biology of human leukocyte antigen
Challenges with HLA–autoimmune disease association
Pathogenesis of celiac disease
Proposed mechanisms of pathogenesis
Generation and function of class I HLA
Generation and function of class II HLA
HLA polymorphism and immune tolerance
Environmental factors impacting HLA polymorphism
Summary

Gregory J. Tsongalis

Gregory J. Tsongalis, PhD, HCLD, CC, FNACB., is the Vice Chair for Research and the Director of the Laboratory for Clinical Genomics and Advanced Technology (CGAT) in the Department of Pathology and Laboratory Medicine at the Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center (NCCC) in Lebanon, NH. He is a Professor of Pathology and Laboratory Medicine at the Audrey and Theodor Geisel School of Medicine at Dartmouth in Hanover, NH and a member of the NCCC Molecular Therapeutics Program and the gastrointestinal and breast cancer clinical oncology groups. In 2016 he became a member of Dartmouth College’s Program in Experimental and Molecular Medicine (PEMM), and he has served on the advisory board of the Health Care Genetics Professional Science Master’s Degree Program and Diagnostic Genetic Sciences Program at the University of Connecticut (Storrs, CT). His area of expertise is in the development and implementation of clinical molecular diagnostic technologies. His research interests are in the pathogenesis of human cancers, personalized medicine and disruptive technologies. He has authored/edited twelve textbooks in the field of molecular pathology, published more than 230 peer reviewed manuscripts, and has been an invited speaker at both national and international meetings. He has served on numerous committees of the American Association for Clinical Chemistry, the American Society for Investigative Pathology, the Federation for American Societies for Experimental Biology, and the Association for Molecular Pathology (where he is a past President). He is active in the Alliance for Clinical Trials in Oncology, the Association for Molecular Pathology, the American Association for Clinical Chemistry, the American Association of Bioanalysts, and the American Society for Investigative Pathology. He serves on the editorial boards of 8 journals including Clinical Chemistry, Experimental and Molecular Pathology, and the Journal of Molecular Diagnostics. In 2016, Dr. Tsongalis received the Norris Cotton Cancer Center Award for Excellence, in 2017 the Association for Molecular Pathology (AMP) Jeffrey A. Kant Leadership Award, and in 2019 the American Society for Investigative Pathology Robbins Distinguished Educator Award. He also serves on numerous corporate scientific advisory boards.

Affiliations and expertise

Laboratory for Clinical Genomics and Advanced Technology (CGAT), Department of Pathology and Laboratory Medicine, Dartmouth, Hitchcock Medical Center and Dartmouth Cancer Center, Lebanon, NH, United States and the Geisel School of Medicine at Dartmouth, Hanover, NH, United States