Impact of Genetics on Mature Lymphoid Leukemias and Lymphomas. 2020

Nathanael G Bailey, and Kojo S J Elenitoba-Johnson
Division of Hematopathology, Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.

Recurrent genetic aberrations have long been recognized in mature lymphoid leukemias and lymphomas. As conventional karyotypic and molecular cloning techniques evolved in the 1970s and 1980s, multiple cytogenetic aberrations were identified in lymphomas, often balanced translocations that juxtaposed oncogenes to the immunoglobulin (IG) or T-cell receptor (TR) loci, leading to dysregulation. However, genetic characterization and classification of lymphoma by conventional cytogenetic methods is limited by the infrequent occurrence of recurrent karyotypic abnormalities in many lymphoma subtypes and by the frequent difficulty in growing clinical lymphoma specimens in culture to obtain informative karyotypes. As higher-resolution genomic techniques developed, such as array comparative genomic hybridization and fluorescence in situ hybridization, many recurrent copy number changes were identified in lymphomas, and copy number assessment of interphase cells became part of routine clinical practice for a subset of diseases. Platforms to globally examine mRNA expression led to major insights into the biology of several lymphomas, although these techniques have not gained widespread application in routine clinical settings. With the advent of next-generation sequencing (NGS) techniques in the early 2000s, numerous insights into the genetic landscape of lymphomas were obtained. In contrast to the myeloid malignancies, most common lymphomas exhibit an at least somewhat mutationally complex genome, with few single driver mutations in the majority of patients. However, many recurrently mutated pathways have been identified across lymphoma subtypes, informing targeted therapeutic approaches that are beginning to make meaningful changes in the treatment of lymphoma. In addition to the ability to identify possible therapeutic targets, NGS techniques are highly amenable to the tracking of residual lymphoma following therapy, because of the presence of unique genetic "fingerprints" in lymphoma cells due to V(D)-J recombination at the antigen receptor loci. This review will provide an overview of the impact of novel genetic technologies on lymphoma classification, biology, and therapy.

UI MeSH Term Description Entries
D007945 Leukemia, Lymphoid Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts. Leukemia, Lymphocytic,Lymphocytic Leukemia,Lymphoid Leukemia,Leukemias, Lymphocytic,Leukemias, Lymphoid,Lymphocytic Leukemias,Lymphoid Leukemias
D008223 Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Germinoblastoma,Lymphoma, Malignant,Reticulolymphosarcoma,Sarcoma, Germinoblastic,Germinoblastic Sarcoma,Germinoblastic Sarcomas,Germinoblastomas,Lymphomas,Lymphomas, Malignant,Malignant Lymphoma,Malignant Lymphomas,Reticulolymphosarcomas,Sarcomas, Germinoblastic
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D002869 Chromosome Aberrations Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS. Autosome Abnormalities,Cytogenetic Aberrations,Abnormalities, Autosome,Abnormalities, Chromosomal,Abnormalities, Chromosome,Chromosomal Aberrations,Chromosome Abnormalities,Cytogenetic Abnormalities,Aberration, Chromosomal,Aberration, Chromosome,Aberration, Cytogenetic,Aberrations, Chromosomal,Aberrations, Chromosome,Aberrations, Cytogenetic,Abnormalities, Cytogenetic,Abnormality, Autosome,Abnormality, Chromosomal,Abnormality, Chromosome,Abnormality, Cytogenetic,Autosome Abnormality,Chromosomal Aberration,Chromosomal Abnormalities,Chromosomal Abnormality,Chromosome Aberration,Chromosome Abnormality,Cytogenetic Aberration,Cytogenetic Abnormality
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D059014 High-Throughput Nucleotide Sequencing Techniques of nucleotide sequence analysis that increase the range, complexity, sensitivity, and accuracy of results by greatly increasing the scale of operations and thus the number of nucleotides, and the number of copies of each nucleotide sequenced. The sequencing may be done by analysis of the synthesis or ligation products, hybridization to preexisting sequences, etc. High-Throughput Sequencing,Illumina Sequencing,Ion Proton Sequencing,Ion Torrent Sequencing,Next-Generation Sequencing,Deep Sequencing,High-Throughput DNA Sequencing,High-Throughput RNA Sequencing,Massively-Parallel Sequencing,Pyrosequencing,DNA Sequencing, High-Throughput,High Throughput DNA Sequencing,High Throughput Nucleotide Sequencing,High Throughput RNA Sequencing,High Throughput Sequencing,Massively Parallel Sequencing,Next Generation Sequencing,Nucleotide Sequencing, High-Throughput,RNA Sequencing, High-Throughput,Sequencing, Deep,Sequencing, High-Throughput,Sequencing, High-Throughput DNA,Sequencing, High-Throughput Nucleotide,Sequencing, High-Throughput RNA,Sequencing, Illumina,Sequencing, Ion Proton,Sequencing, Ion Torrent,Sequencing, Massively-Parallel,Sequencing, Next-Generation

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