Genomic Medicine. A Practical Guide

✍ Scribed by Laura J. Tafe, Maria E. Arcila (eds.)

• Publisher: Springer
• Year: 2020
• Tongue: English
• Leaves: 323
• Category: Library

✦ Table of Contents

Preface
Contents
Contributors
Part I: General Concepts
Chapter 1: Pre-analytics, Current Testing Technologies, and Limitations of Testing
Introduction
Pre-analytic Variables in Surgical Pathology
Prefixation
Fixation
Decalcification
Processing and Storage
Tissue Stewardship
RNA Pre-analytic Considerations
Pre-analytics of Circulating Tumor DNA or Cell-Free DNA
Landscape of Current Testing Technologies
Tests to Detect Chromosomal Abnormalities
Karyotyping (G-Banding)
Fluorescence In Situ Hybridization
Reverse Transcription Polymerase Chain Reaction
Multiplex Ligation-Dependent Probe Amplification
Array Comparative Genomic Hybridization (aCGH) and Single-Nucleotide Polymorphism (SNP) Arrays
Methods Used to Detect Changes in the DNA Sequence
Allele-Specific PCR
Sanger Sequencing with Capillary Electrophoresis
Pyrosequencing
Melting Curve Analysis
Next-Generation Sequencing
Gene Expression Profiling
References
Chapter 2: Next-Generation Sequencing
Introduction
Library Preparation
Nucleic Acid Isolation
Fragmentation
End Repair
Adapter Ligation
Size Selection
Target Enrichment
Amplification
Quantitation and Quality Assessment
Library Pooling
Additional Steps
Sequencing
Short-Read Sequencers (<1000 Nucleotides)
Long-Read Sequencing (>1000 Nucleotides)
Informatics Process
Base Calls
Demultiplexing
FASTQ Files
Sequence Assembly
Alignment
Variant Calling
Variant Filtering
Variant Annotation
Variant Prioritization
Clinical Reporting
Flow and Storage of Data
Clinical Applications of NGS
Conclusion
References
Chapter 3: Cell-Free DNA Testing
Introduction
Current Applications: Noninvasive Prenatal Testing
Current Applications: Solid Organ Transplantation
Current Applications: Cancer
Pre-analytical Considerations
cfDNA Biology
Specimen Type
Collection and Processing
cfDNA Detection and Quantification Technologies
Limitations
Future Directions
References
Chapter 4: Role of Bioinformatics in Molecular Medicine
Introduction
Central Dogma of NGS Bioinformatics
FASTA/FASTQ
Alignment
BAM/SAM
Variant Calling
Variant Call Format (VCF) File
Variant Annotation and Prioritization
Regulatory Considerations
Advanced Applications
Copy Number Alterations
Structural Variants
Microsatellite Instability
References
Chapter 5: Interpreting Genomic Reports
Introduction
Reporting Sequence Variants
Elements of the Molecular Pathology Report
Elements Unique to Genomic Reports
Variant Categorization
Gene and Sequence Variant Nomenclature
Mutation, Polymorphism, and Variants
Interpretation
Germline Variants
Somatic Variants
References
Part II: Applications in Solid Tumors
Chapter 6: Lung Carcinoma
Introduction
Alterations with Already Approved Targeted Therapies
EGFR Mutations
ALK Fusions
ROS1 Fusions
BRAF Mutations
NTRK Fusions
KRAS Mutations
HER2 Mutations
MET Alterations
RET Fusions
PIK3CA Mutations
MAP2K1/MEK1 Mutations
FGFR3 Alterations
Acquired Resistance Mechanisms to TKIs
Molecular Testing Guidelines for Therapy Selection
Conclusions
References
Chapter 7: GI Including GIST
Introduction
Microsatellite Instability in Colorectal and Gastric Adenocarcinomas
MLH1 Promoter Hypermethylation in CRC
RAS Mutations in CRC
BRAF Alterations in CRC
HER2 Alterations in Upper Gastrointestinal Adenocarcinomas and CRC
PIK3CA Mutations in CRC
Other Emerging Biomarkers in CRC and Upper Gastrointestinal Adenocarcinomas
MET Amplification
EGFR Alterations
MAP2K1 Mutations
FGFR Alterations
NTRK Rearrangements
RET, ALK, and ROS1 Rearrangements
Mutational Testing in Gastrointestinal Stromal Tumors
KIT and PDGFRA Mutant GISTs
KIT/PDGFRA-Negative GISTs
Molecular Testing for Familial Syndromes
References
Chapter 8: Breast
Introduction
Molecular Diagnostics in Breast Cancer
Resistance Mechanisms in Breast Cancer
For the Practicing Clinician
References
Chapter 9: Genitourinary Tumors
Introduction
Prostate
Molecular Diagnostics in Prostate Cancer
Prognostic Molecular Assays in PCa
Targets of Therapy and Predictive Molecular Markers
Bladder
Molecular Diagnostics in Bladder Cancer
Diagnostic Assays
Genomic Taxonomy, Targets of Therapy, and Predictive Markers
References
Chapter 10: Gynecologic Malignancies
Introduction
Ovary
Endometrial Cancer
Uterine Mesenchymal Tumors
References
Chapter 11: Sarcomas
Introduction
Sarcomas with Recurrent Translocations (Table 11.1)
Benign Mesenchymal Neoplasms with Recurrent Translocations (Table 11.2)
Adipocytic Neoplasms (Tables 11.3 and 11.4)
Vascular Tumors (Table 11.5)
Tumors with Recurrent Gene Fusions (Including EWSR1) and Other Alterations (Tables 11.6, 11.7, 11.8, 11.9, 11.10, 11.11, and 11.12)
Selected References
Chapter 12: Salivary Gland Carcinomas
Introduction
Mucoepidermoid Carcinoma
Phenotype
Genetics and Clinical Utility
Adenoid Cystic Carcinoma
Phenotype
Genetics and Clinical Utility
Secretory Carcinoma of Salivary Gland
Phenotype
Genetics and Clinical Utility
Clear Cell Carcinoma
Phenotype
Genetics and Clinical Utility
Myoepithelial Carcinoma
Phenotype
Genetics and Clinical Utility
Polymorphous Adenocarcinoma and Cribriform Adenocarcinoma of Minor Salivary Gland
Phenotype
Genetics and Clinical Utility
Salivary Duct Carcinoma
Phenotype
Genetics and Clinical Utility
Intraductal Carcinoma
Phenotype
Genetics and Clinical Utility
References
Chapter 13: Sinonasal Carcinomas
Introduction
NUT Carcinoma
Phenotype
Genetics and Clinical Utility
SMARCB1-Deficient Sinonasal Carcinoma
Phenotype
Genetics and Clinical Utility
Sinonasal Undifferentiated Carcinoma and Large Cell Neuroendocrine Carcinoma
Phenotype
Genetics and Clinical Utility
Sinonasal Squamous Cell Carcinomas and Adenocarcinomas with Genetic Signatures
References
Part III: Applications in Hematopathology
Chapter 14: Acute Myeloid Neoplasms
Introduction
A Standard Genetic Workup
AML with Recurrent Genetic Aberrancies
Core Binding Factor AML (Tables 14.2 and 14.3)
Acute Promyelocytic Leukemia (APL) (Table 14.4)
AML with t(9;11)(p21.3;q23.3), KMT2A-MLLT3 (Table 14.5)
AML with t(6;9)(p23;q34.1), DEK-NUP214 (Table 14.6)
AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM (Table 14.7)
AML (Megakaryoblastic) with t(1;22)(p13.3;q13.1), RBM15-MRTFA (Table 14.8)
AML with Mutated NPM1 (Table 14.9)
AML with Biallelic Mutations of CEBPA (Table 14.10)
Provisional 2016 WHO AML with Recurrent Genetic Abnormality Subtypes
AML with Myelodysplasia-Related Changes
Therapy-Related Myeloid Neoplasms
Myeloid Neoplasms with Germline Predisposition and AML in Children
Myeloid Neoplasms with Germline Predisposition
Transient Abnormal Myelopoiesis and Myeloid Leukemia Associated with Down Syndrome
Childhood AML
References
Chapter 15: Chronic Myeloid Neoplasms
Introduction
Myeloproliferative Neoplasms (MPNs)
Mastocytosis
Myeloid/Lymphoid Neoplasms with Eosinophilia and Gene Rearrangements
Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)
Myelodysplastic Syndrome (MDS)
References
Chapter 16: Lymphomas
Introduction
Recurrent Molecular Aberrancies in B-Cell Neoplasms
Hodgkin Lymphoma (HL)
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
Mantle Cell Lymphoma (MCL)
Extranodal Marginal Zone Lymphoma (Extranodal MZL, Mucosa-Associated Lymphoid Tissue Lymphoma, MALT)
Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia (LPL/WM)
Hairy Cell Leukemia (HCL)
Follicular Lymphoma (FL)
Diffuse Large B-Cell Lymphoma (DLBCL) and Other High-Grade B-Cell Lymphomas (HGBCL)
Burkitt’s Lymphoma (BL)
Recurrent Molecular Aberrancies in T-Cell Neoplasms
Angioimmunoblastic T-Cell Lymphoma (AITL) and Other Nodal T-Cell Lymphomas with T-Follicular Helper (TFH) Phenotype
Anaplastic Large-Cell Lymphoma (ALCL)
Peripheral T-Cell Lymphoma, Not Otherwise Specified (PTCL, NOS)
T-Cell Large Granular Lymphocytic (T-LGL) Leukemia
T-Cell Prolymphocytic Leukemia (T-PLL)
Enteropathy-Associated T-Cell Lymphoma (EATL) and Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma (MEITL)
Adult T-Cell Leukemia/Lymphoma (ATLL)
Extranodal Natural Killer/T-Cell Lymphoma (ENKTL)
References
Index