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Cancer Genetics and Cytogenetics May 1986The quantitative aspects of Bloom's syndrome cytogenetics are reviewed. The most characteristic feature is an increased rate of homologous chromatid exchange, both... (Review)
Review
The quantitative aspects of Bloom's syndrome cytogenetics are reviewed. The most characteristic feature is an increased rate of homologous chromatid exchange, both sister chromatid exchange and mitotic crossing-over. Other phenomena are a tendency of somatic cells to fuse, an increased rate of chromosome breaks, often with sister chromatid reunion, formation of nonhomologous quadriradials, and occurrence of allocyclic and triradial chromosomes. Mitotic chiasmata are situated highly nonrandomly, preferably in Q-dark regions. Chromosomes containing chiasma "hot-spots" appear to contain more active genes than similarly sized control chromosomes. They also contain a high proportion of localized oncogenes. Bloom's syndrome homozygotes show a high incidence of cancer (1/4). This may depend on a) the high rate of homozygosity resulting from mitotic crossing-over, which would allow the expression of recessive cancer genes; b) unequal crossing-over would amplify these genes; c) chromosome structural changes that might transfer oncogenes to new locations and, thus, activate them; and d) immunodeficiency, which would promote malignant growth.
Topics: Bloom Syndrome; Bone Marrow; Cells, Cultured; Chromosome Aberrations; Chromosome Banding; Crossing Over, Genetic; Fibroblasts; Genetic Markers; Humans; Karyotyping; Lymphocytes; Mitosis; Oncogenes; Precancerous Conditions; Risk; Sister Chromatid Exchange
PubMed: 3513946
DOI: 10.1016/0165-4608(86)90132-9 -
Pediatrics International : Official... Jan 2022
Topics: Bloom Syndrome; Early Diagnosis; Female; Humans; Karyotyping; Pregnancy; Prenatal Diagnosis
PubMed: 35278254
DOI: 10.1111/ped.15020 -
Nihon Rinsho. Japanese Journal of... Sep 2006
Review
Topics: Adenosine Triphosphatases; Bloom Syndrome; DNA Helicases; DNA Repair; Diagnosis, Differential; Humans; Mutation; Prognosis; RecQ Helicases
PubMed: 17022574
DOI: No ID Found -
Cell Death & Disease Apr 2022RecQ helicases-also known as the "guardians of the genome"-play crucial roles in genome integrity maintenance through their involvement in various DNA metabolic...
RecQ helicases-also known as the "guardians of the genome"-play crucial roles in genome integrity maintenance through their involvement in various DNA metabolic pathways. Aside from being conserved from bacteria to vertebrates, their importance is also reflected in the fact that in humans impaired function of multiple RecQ helicase orthologs are known to cause severe sets of problems, including Bloom, Werner, or Rothmund-Thomson syndromes. Our aim was to create and characterize a zebrafish (Danio rerio) disease model for Bloom syndrome, a recessive autosomal disorder. In humans, this syndrome is characterized by short stature, skin rashes, reduced fertility, increased risk of carcinogenesis, and shortened life expectancy brought on by genomic instability. We show that zebrafish blm mutants recapitulate major hallmarks of the human disease, such as shortened lifespan and reduced fertility. Moreover, similarly to other factors involved in DNA repair, some functions of zebrafish Blm bear additional importance in germ line development, and consequently in sex differentiation. Unlike fanc genes and rad51, however, blm appears to affect its function independent of tp53. Therefore, our model will be a valuable tool for further understanding the developmental and molecular attributes of this rare disease, along with providing novel insights into the role of genome maintenance proteins in somatic DNA repair and fertility.
Topics: Animals; Bloom Syndrome; Germ Cells; Longevity; RecQ Helicases; Zebrafish
PubMed: 35436990
DOI: 10.1038/s41419-022-04815-8 -
International Journal of Surgery... Mar 2023
Topics: Humans; Bloom Syndrome; Mouth Neoplasms; Precancerous Conditions
PubMed: 36928777
DOI: 10.1097/JS9.0000000000000009 -
Pediatric Blood & Cancer Nov 2023
Topics: Humans; Bloom Syndrome; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation
PubMed: 37644665
DOI: 10.1002/pbc.30655 -
Redox Biology Apr 2017Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme... (Review)
Review
Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis. Recent studies indicate new, alternative sources of oxidative stress in A-T, BS and NBS cells, including NADPH oxidase 4 (NOX4), oxidised low-density lipoprotein (ox-LDL) or Poly (ADP-ribose) polymerases (PARP). Mitochondrial abnormalities such as changes in the ultrastructure and function of mitochondria, excess mROS production as well as mitochondrial damage have also been reported in A-T, BS and NBS cells. A-T, BS and NBS cells are inextricably linked to high levels of reactive oxygen species (ROS), and thereby, chronic oxidative stress may be a major phenotypic hallmark in these diseases. Due to the presence of mitochondrial disturbances, A-T, BS and NBS may be considered mitochondrial diseases. Excess activity of antioxidant enzymes and an insufficient amount of low molecular weight antioxidants indicate new pharmacological strategies for patients suffering from the aforementioned diseases. However, at the current stage of research we are unable to ascertain if antioxidants and free radical scavengers can improve the condition or prolong the survival time of A-T, BS and NBS patients. Therefore, it is necessary to conduct experimental studies in a human model.
Topics: Ataxia Telangiectasia; Bloom Syndrome; DNA Damage; DNA Repair; Gene Expression Regulation; Humans; Lipoproteins, LDL; Mitochondria; NADPH Oxidase 4; Nijmegen Breakage Syndrome; Oxidative Stress; Poly(ADP-ribose) Polymerases; Reactive Oxygen Species; Signal Transduction
PubMed: 28063379
DOI: 10.1016/j.redox.2016.12.030 -
Scientific Reports Jan 2021Bloom Syndrome (BS; OMIM #210900; ORPHA #125) is a rare genetic disorder that is associated with growth deficits, compromised immune system, insulin resistance, genome...
Bloom Syndrome (BS; OMIM #210900; ORPHA #125) is a rare genetic disorder that is associated with growth deficits, compromised immune system, insulin resistance, genome instability and extraordinary predisposition to cancer. Most efforts thus far have focused on understanding the role of the Bloom syndrome DNA helicase BLM as a recombination factor in maintaining genome stability and suppressing cancer. Here, we observed increased levels of reactive oxygen species (ROS) and DNA base damage in BLM-deficient cells, as well as oxidative-stress-dependent reduction in DNA replication speed. BLM-deficient cells exhibited increased mitochondrial mass, upregulation of mitochondrial transcription factor A (TFAM), higher ATP levels and increased respiratory reserve capacity. Cyclin B1, which acts in complex with cyclin-dependent kinase CDK1 to regulate mitotic entry and associated mitochondrial fission by phosphorylating mitochondrial fission protein Drp1, fails to be fully degraded in BLM-deficient cells and shows unscheduled expression in G1 phase cells. This failure to degrade cyclin B1 is accompanied by increased levels and persistent activation of Drp1 throughout mitosis and into G1 phase as well as mitochondrial fragmentation. This study identifies mitochondria-associated abnormalities in Bloom syndrome patient-derived and BLM-knockout cells and we discuss how these abnormalities may contribute to Bloom syndrome.
Topics: Autophagy; Bloom Syndrome; Cyclin B1; DNA Damage; DNA Replication; DNA-Binding Proteins; Energy Metabolism; Fibroblasts; G1 Phase; Humans; Mitochondria; Mitochondrial Proteins; Mitosis; Oxidative Stress; Reactive Oxygen Species; RecQ Helicases; Transcription Factors; Up-Regulation
PubMed: 33495511
DOI: 10.1038/s41598-021-81075-0 -
Journal of Clinical Immunology Jan 2018Bloom's syndrome (BS) is an autosomal recessive disease, caused by mutations in the BLM gene. This gene codes for BLM protein, which is a helicase involved in DNA...
Bloom's syndrome (BS) is an autosomal recessive disease, caused by mutations in the BLM gene. This gene codes for BLM protein, which is a helicase involved in DNA repair. DNA repair is especially important for the development and maturation of the T and B cells. Since BLM is involved in DNA repair, we aimed to study if BLM deficiency affects T and B cell development and especially somatic hypermutation (SHM) and class switch recombination (CSR) processes. Clinical data of six BS patients was collected, and immunoglobulin serum levels were measured at different time points. In addition, we performed immune phenotyping of the B and T cells and analyzed the SHM and CSR in detail by analyzing IGHA and IGHG transcripts using next-generation sequencing. The serum immunoglobulin levels were relatively low, and patients had an increased number of infections. The absolute number of T, B, and NK cells were low but still in the normal range. Remarkably, all BS patients studied had a high percentage (20-80%) of CD4+ and CD8+ effector memory T cells. The process of SHM seems normal; however, the Ig subclass distribution was not normal, since the BS patients had more IGHG1 and IGHG3 transcripts. In conclusion, BS patients have low number of lymphocytes, but the immunodeficiency seems relatively mild since they have no severe or opportunistic infections. Most changes in the B cell development were seen in the CSR process; however, further studies are necessary to elucidate the exact role of BLM in CSR.
Topics: Adult; B-Lymphocytes; Bloom Syndrome; Cell Differentiation; Child; DNA Repair; Female; Humans; Immunoglobulin A; Immunoglobulin Class Switching; Immunoglobulin G; Immunologic Deficiency Syndromes; Immunophenotyping; Lymphocyte Activation; Male; Middle Aged; Mutation; RecQ Helicases; Somatic Hypermutation, Immunoglobulin; T-Lymphocytes
PubMed: 29098565
DOI: 10.1007/s10875-017-0454-y -
BioEssays : News and Reviews in... May 1992This article focuses upon defining those factors which may contribute to the pathogenesis of cancer. The molecular basis of tumour etiology is discussed with reference... (Review)
Review
This article focuses upon defining those factors which may contribute to the pathogenesis of cancer. The molecular basis of tumour etiology is discussed with reference to cancer predisposing syndromes, and in particular to the human inherited disease, Bloom's syndrome. In Bloom's syndrome, patients are predisposed to a wide variety of malignant disease. We propose a model in which overexpression of the ubiquitous c-myc proto-oncogene contributes to this process.
Topics: Bloom Syndrome; DNA Damage; Gene Expression Regulation, Neoplastic; Genes, myc; Humans; Models, Biological; Neoplastic Syndromes, Hereditary; Proto-Oncogene Mas
PubMed: 1637364
DOI: 10.1002/bies.950140508