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Acta Medica Academica Apr 2019The aim of this review is to summarize the current knowledge of genomic information in multiple myeloma. Multiple myeloma is a genetically complex plasma cell neoplasm... (Review)
Review
The aim of this review is to summarize the current knowledge of genomic information in multiple myeloma. Multiple myeloma is a genetically complex plasma cell neoplasm that evolves from pre-malignant stages following genomic evolution leading to the proliferation of malignant plasma cells and the production of monoclonal immunoglobulin. The outcomes of patients with myeloma have dramatically improved over the past decade with the introduction of novel agents. Nevertheless, the disease is considered incurable and displays considerable heterogeneity in clinical presentation, course and survival. This heterogeneity can often be traced to cytogenetic abnormalities in the malignant clone. Accordingly, a large body of literature has examined the impact of genomics on myeloma and risk stratification based on cytogenetics has been adopted. In this review, we will focus on the cytogenetics of multiple myeloma and the prognostic significance as well as possible predictive implications. We will briefly review the existing methodologies relevant to myeloma but explore in greater depth the more novel molecular tools as applied to this disease. CONCLUSION: The field of genomics in multiple myeloma is rapidly evolving however more translational research is needed to accurately use genomic data as a tool of precision medicine.
Topics: Chromosome Aberrations; Cytogenetics; Genomics; Humans; Multiple Myeloma; Prognosis
PubMed: 31264433
DOI: 10.5644/ama2006-124.242 -
Blood Advances May 2023Risk stratification in acute myeloid leukemia (AML) remains principle in survival prognostication and treatment selection. The 2022 European LeukemiaNet (ELN)...
Risk stratification in acute myeloid leukemia (AML) remains principle in survival prognostication and treatment selection. The 2022 European LeukemiaNet (ELN) recommendations were recently published, with notable updates to risk group assignment. The complexity of risk stratification and comparative outcomes between the 2022 and 2017 ELN guidelines remains unknown. This comparative analysis evaluated outcomes between the 2017 and 2022 ELN criteria in patients enrolled within the multicenter Beat AML cohort. Five hundred thirteen patients were included. Most patients had 1 or 2 ELN risk-defining abnormalities. In patients with ≥2 ELN risk-defining mutations, 44% (n = 132) had mutations spanning multiple ELN risk categories. Compared with ELN 2017 criteria, the updated ELN 2022 guidelines changed the assigned risk group in 15% of patients, including 10%, 26%, and 6% of patients categorized as being at ELN 2017 favorable-, intermediate-, and adverse-risk, respectively. The median overall survival across ELN 2022 favorable-, intermediate-, and adverse-risk groups was not reached, 16.8, and 9.7 months, respectively. The ELN 2022 guidelines more accurately stratified survival between patients with intermediate- or adverse-risk AML treated with induction chemotherapy compared with ELN 2017 guidelines. The updated ELN 2022 guidelines better stratify survival between patients with intermediate- or adverse-risk AML treated with induction chemotherapy. The increased complexity of risk stratification with inclusion of additional cytogenetic and molecular aberrations necessitates clinical workflows simplifying risk stratification.
Topics: Humans; Leukemia, Myeloid, Acute; Risk Factors; Mutation; Cytogenetics; Induction Chemotherapy
PubMed: 36441905
DOI: 10.1182/bloodadvances.2022009010 -
Genes Jun 2021Fish is the most species-rich class of vertebrates, including a number of species that correspond to about half of the total vertebrates [...].
Fish is the most species-rich class of vertebrates, including a number of species that correspond to about half of the total vertebrates [...].
Topics: Animals; Chromosome Aberrations; Cytogenetics; Fishes; In Situ Hybridization, Fluorescence; Karyotyping
PubMed: 34203124
DOI: 10.3390/genes12070983 -
Cytogenetic and Genome Research 2021
Topics: Chromosome Aberrations; Chromosome Banding; Cytogenetic Analysis; Cytogenetics; Humans
PubMed: 34407536
DOI: 10.1159/000516654 -
American Journal of Hematology Dec 2021While Waldenström macroglobulinemia (WM) is characterized by an almost unifying mutation in MYD88, clinical presentation at diagnosis and response to therapy can be...
While Waldenström macroglobulinemia (WM) is characterized by an almost unifying mutation in MYD88, clinical presentation at diagnosis and response to therapy can be widely different among WM patients. Current prognostic tools only partially address this clinical heterogeneity. Limited data compiling both molecular and cytogenetic information have been used in risk prognostication in WM. To investigate the clinical impact of genetic alterations in WM, we evaluated cytogenetic and molecular abnormalities by chromosome banding analyses, FISH and targeted NGS in a retrospective cohort of 239 WM patients, including 187 patients treated by first-line chemotherapy or immunochemotherapy. Most frequent mutations were identified in MYD88 (93%), CXCR4 (29%), MLL2 (11%), ARID1A (8%), TP53 (8%), CD79A/B (6%), TBL1XR1 (4%) and SPI1 (4%). The median number of cytogenetic abnormalities was two (range, 0-22). Main cytogenetic abnormalities were 6q deletion (del6q) (27%), trisomy 4 (tri4) (12%), tri18 (11%), del13q (11%), tri12 (7.5%) and del17p (7%). Complex karyotype (CK) was observed in 15% (n = 31) of cases, including 5% (n = 12) of highly CK (high-CK). TP53 abnormalities (TP53abn) were present in 15% of evaluable patients. TP53abn and del6q were associated with CK/high-CK (p < .05). Fifty-three percent of patients with hyperviscosity harbored CXCR4 mutations. Cytogenetic and molecular abnormalities did not significantly impact time to first treatment and response to therapy. Prognostic factors associated with shorter PFS were del6q (p = .01), TP53abn (p = .002) and high-CK (p = .01). These same factors as well as IPSSWM, tri4, CXCR4 frameshift and SPI1 mutations were significantly associated with lower OS (p < .05). These results argue for integration of both cytogenetic and molecular screening in evaluation of first-line WM patients.
Topics: Adult; Aged; Aged, 80 and over; Chromosome Aberrations; Cytogenetics; Female; Humans; Male; Middle Aged; Mutation; Prognosis; Retrospective Studies; Waldenstrom Macroglobulinemia
PubMed: 34462944
DOI: 10.1002/ajh.26339 -
Proceedings of the National Academy of... Sep 2023Isochromosomes are mirror-imaged chromosomes with simultaneous duplication and deletion of genetic material which may contain two centromeres to create isodicentric...
Isochromosomes are mirror-imaged chromosomes with simultaneous duplication and deletion of genetic material which may contain two centromeres to create isodicentric chromosomes. Although isochromosomes commonly occur in cancer and developmental disorders and promote genome instability, mechanisms that prevent isochromosomes are not well understood. We show here that the tumor suppressor and methyltransferase SETD2 is essential to prevent these errors. Using cellular and cytogenetic approaches, we demonstrate that loss of SETD2 or its epigenetic mark, histone H3 lysine 36 trimethylation (H3K36me3), results in the formation of isochromosomes as well as isodicentric and acentric chromosomes. These defects arise during DNA replication and are likely due to faulty homologous recombination by RAD52. These data provide a mechanism for isochromosome generation and demonstrate that SETD2 and H3K36me3 are essential to prevent the formation of this common mutable chromatin structure known to initiate a cascade of genomic instability in cancer.
Topics: Humans; Centromere; Chromosome Aberrations; Cytogenetics; DNA Replication; Genomic Instability; Isochromosomes
PubMed: 37722039
DOI: 10.1073/pnas.2303752120 -
American Journal of Hematology Mar 2017Acute myeloid leukemia (AML) is characterized by a clonal expansion of undifferentiated myeloid precursors resulting in impaired hematopoiesis and bone marrow failure.... (Review)
Review
Acute myeloid leukemia (AML) is characterized by a clonal expansion of undifferentiated myeloid precursors resulting in impaired hematopoiesis and bone marrow failure. In 2016, the World Health Organization (WHO) published revisions to the classification of myeloid neoplasms and acute leukemias. Similar to the 2008 classification, the updated classification incorporates clinical features, morphology, immunophenotyping, and cytogenetics, with greater emphasis on molecular genetics, to define disease entities. This brief review addresses the various components of pathologic assessment to establish a diagnosis of AML and to help risk stratify patients, with an emphasis on newer techniques used in the detection of mutations with prognostic significance, as well as assays employed in the evaluation of minimal residual disease following treatment.
Topics: Classification; Cytogenetics; Humans; Immunophenotyping; Leukemia, Myeloid, Acute; Molecular Biology; Neoplasm, Residual; Risk Assessment; World Health Organization
PubMed: 28066929
DOI: 10.1002/ajh.24648 -
Chromosome Research : An International... Mar 2020As a scientist, one’s perspective of the human genome is informed by the way it is studied – at the level of single nucleotides, a single gene, a specific genomic...
As a scientist, one’s perspective of the human genome is informed by the way it is studied – at the level of single nucleotides, a single gene, a specific genomic region, an entire chromosome, the complete karyotype, or the nucleus that encompasses both the genome and the nuclear components that support genome structure, function, stability, and inheritance. Experimentally investigating aspects of genome structure and chromosome number and higher order packaging requires different technical approaches that offer varying levels of resolution. This special issue of Chromosome Research provides overviews of a few current methodologies to study chromosome and genome organization and function, with a particular focus on contemporary sequencing-based approaches.
Topics: Animals; Chromosomes; Cytogenetics; Genome; Genomics; Humans
PubMed: 32157563
DOI: 10.1007/s10577-020-09629-y -
Haematologica Oct 2018
Topics: Cytogenetics; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 30270204
DOI: 10.3324/haematol.2018.200311 -
International Journal of Molecular... Feb 2019The concept of "chromosomics" was introduced by Prof. Uwe Claussen in 2005. Herein, the growing insights into human chromosome structure finally lead to a "chromosomic... (Review)
Review
BACKGROUND
The concept of "chromosomics" was introduced by Prof. Uwe Claussen in 2005. Herein, the growing insights into human chromosome structure finally lead to a "chromosomic view" of the three-dimensional constitution and plasticity of genes in interphase nuclei are discussed. This review is dedicated to the memory of Prof. Uwe Claussen (30 April 1945⁻20 July 2008).
RECENT FINDINGS
Chromosomics is the study of chromosomes, their three-dimensional positioning in the interphase nucleus, the consequences from plasticity of chromosomal subregions and gene interactions, the influence of chromatin-modification-mediated events on cells, and even individuals, evolution, and disease. Progress achieved in recent years is summarized, including the detection of chromosome-chromosome-interactions which, if damaged, lead to malfunction and disease. However, chromosomics in the Human Genetics field is not progressing presently, as research interest has shifted from single cell to high throughput, genomic approaches.
CONCLUSION
Chromosomics and its impact were predicted correctly in 2005 by Prof. Claussen. Although some progress was achieved, present reconsiderations of the role of the chromosome and the single cell in Human Genetic research are urgently necessary.
Topics: Cell Nucleus; Chromosomes, Human; Cytogenetics; Genome, Human; Genomics; Humans
PubMed: 30769866
DOI: 10.3390/ijms20040826