Journal Article FZJ-2022-02210

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Recurrent Germline Variant in RAD21 Predisposes Children to Lymphoblastic Leukemia or Lymphoma

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2022
Molecular Diversity Preservation International Basel

International journal of molecular sciences 23(9), 5174 - () [10.3390/ijms23095174]

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Abstract: Somatic loss of function mutations in cohesin genes are frequently associated with various cancer types, while cohesin disruption in the germline causes cohesinopathies such as Cornelia-de-Lange syndrome (CdLS). Here, we present the discovery of a recurrent heterozygous RAD21 germline aberration at amino acid position 298 (p.P298S/A) identified in three children with lymphoblastic leukemia or lymphoma in a total dataset of 482 pediatric cancer patients. While RAD21 p.P298S/A did not disrupt the formation of the cohesin complex, it altered RAD21 gene expression, DNA damage response and primary patient fibroblasts showed increased G2/M arrest after irradiation and Mitomycin-C treatment. Subsequent single-cell RNA-sequencing analysis of healthy human bone marrow confirmed the upregulation of distinct cohesin gene patterns during hematopoiesis, highlighting the importance of RAD21 expression within proliferating B- and T-cells. Our clinical and functional data therefore suggest that RAD21 germline variants can predispose to childhood lymphoblastic leukemia or lymphoma without displaying a CdLS phenotype

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Contributing Institute(s):
  1. Bioinformatik (IBG-4)
  2. Jülich Supercomputing Center (JSC)
  3. John von Neumann - Institut für Computing (NIC)
  4. Strukturbiochemie (IBI-7)
Research Program(s):
  1. 5111 - Domain-Specific Simulation & Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) (POF4-511)
  2. 2171 - Biological and environmental resources for sustainable use (POF4-217) (POF4-217)
  3. Forschergruppe Gohlke (hkf7_20200501) (hkf7_20200501)
  4. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)

Appears in the scientific report 2022
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Medline ; Creative Commons Attribution CC BY 4.0 ; DOAJ ; OpenAccess ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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Document types > Articles > Journal Article
Institute Collections > IBI > IBI-7
Institute Collections > IBG > IBG-4
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Institute Collections > JSC
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Open Access
NIC

 Record created 2022-05-19, last modified 2023-01-28


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