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@ARTICLE{Berg:301538,
author = {V. Berg and A. Lollies and M. Schneider and P. Johansson
and M. A. Weniger and E. Albertini and F. Facchetti and S.
Ascani and A. Moawia and S. Bens and A. Fischer and R.
Siebert and W. Klapper and L. Lorenzi and E. Tiacci and S.
Hartmann and B. Budeus and M.-L. Hansmann and R.
Küppers$^*$},
title = {{C}ommon origin and somatic mutation patterns of composite
lymphomas and leukemias.},
journal = {Leukemia},
volume = {39},
number = {8},
issn = {0887-6924},
address = {London},
publisher = {Springer Nature},
reportid = {DKFZ-2025-01059},
pages = {1960-1971},
year = {2025},
note = {2025 Aug;39(8):1960-1971},
abstract = {When two lymphomas occur concurrently or sequentially in a
patient, it is a major question whether they derive from the
same lymphocyte or hematopoietic precursor cell or developed
independently. We studied four composite classic Hodgkin
lymphomas (HL) and other mature B-cell lymphomas, and two
composite mature B- and T-cell neoplasias by whole exome
sequencing (WES). Analysis of their IGV genes revealed that
three composite B-cell lymphomas originated from common
germinal center-experienced B cells. WES identified shared
somatic mutations in the lymphomas of these clonally related
composite lymphomas, indicating their derivation from a
common, pre-malignant precursor. Most mutations were
restricted to one or the other of these lymphomas, likely
explaining how distinct lymphomas developed from a common
ancestral B cell. In the two B-cell/T-cell lymphoma cases,
and a composite clonally unrelated HL/chronic lymphocytic
leukemia, the lymphoma partners did not share any somatic
mutations. In three cases, we identified potentially
oncogenic variants also in cells serving as constitutional
controls. These variants may have contributed to development
of a composite lymphoma/leukemia. We provide additional
evidence of frequent clonal relation in composite lymphomas,
highlight the multistep transformation process of related
lymphomas with a likely pre-malignant intermediate common
precursor, and support the importance of constitutional
variants in lymphomagenesis.},
cin = {ED01},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40404986},
doi = {10.1038/s41375-025-02549-y},
url = {https://inrepo02.dkfz.de/record/301538},
}