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@ARTICLE{Schedel:907781,
author = {Schedel, Anne and Friedrich, Ulrike Anne and Morcos, Mina
N. F. and Wagener, Rabea and Mehtonen, Juha and Watrin,
Titus and Saitta, Claudia and Brozou, Triantafyllia and
Michler, Pia and Walter, Carolin and Försti, Asta and
Baksi, Arka and Menzel, Maria and Horak, Peter and
Paramasivam, Nagarajan and Fazio, Grazia and Autry, Robert J
and Fröhling, Stefan and Suttorp, Meinolf and Gertzen,
Christoph and Gohlke, Holger and Bhatia, Sanil and Wadt,
Karin and Schmiegelow, Kjeld and Dugas, Martin and Richter,
Daniela and Glimm, Hanno and Heinäniemi, Merja and
Jessberger, Rolf and Cazzaniga, Gianni and Borkhardt, Arndt
and Hauer, Julia and Auer, Franziska},
title = {{R}ecurrent {G}ermline {V}ariant in {RAD}21 {P}redisposes
{C}hildren to {L}ymphoblastic {L}eukemia or {L}ymphoma},
journal = {International journal of molecular sciences},
volume = {23},
number = {9},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {FZJ-2022-02210},
pages = {5174 -},
year = {2022},
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},
cin = {IBG-4 / JSC / NIC / IBI-7},
ddc = {540},
cid = {I:(DE-Juel1)IBG-4-20200403 / I:(DE-Juel1)JSC-20090406 /
I:(DE-Juel1)NIC-20090406 / I:(DE-Juel1)IBI-7-20200312},
pnm = {5111 - Domain-Specific Simulation $\&$ Data Life Cycle Labs
(SDLs) and Research Groups (POF4-511) / 2171 - Biological
and environmental resources for sustainable use (POF4-217) /
Forschergruppe Gohlke $(hkf7_20200501)$ / 5241 - Molecular
Information Processing in Cellular Systems (POF4-524)},
pid = {G:(DE-HGF)POF4-5111 / G:(DE-HGF)POF4-2171 /
$G:(DE-Juel1)hkf7_20200501$ / G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35563565},
UT = {WOS:000794632900001},
doi = {10.3390/ijms23095174},
url = {https://juser.fz-juelich.de/record/907781},
}