Large B-cell lymphomas with CCND1 rearrangement have different immunoglobulin gene breakpoints and genomic profile than mantle cell lymphoma
Mantle cell lymphoma (MCL) is genetically characterized by the IG :: CCND1 translocation mediated by an aberrant V(D)J rearrangement. CCND1 translocations and overexpression have been identified in occasional aggressive B-cell lymphomas with unusual features for MCL. The mechanism generating CCND1 r...
Saved in:
Published in | Blood cancer journal (New York) Vol. 14; no. 1; pp. 166 - 10 |
---|---|
Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
23.09.2024
Springer Nature B.V Nature Publishing Group |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Mantle cell lymphoma (MCL) is genetically characterized by the
IG
::
CCND1
translocation mediated by an aberrant V(D)J rearrangement.
CCND1
translocations and overexpression have been identified in occasional aggressive B-cell lymphomas with unusual features for MCL. The mechanism generating
CCND1
rearrangements in these tumors and their genomic profile are not known. We have reconstructed the
IG
::
CCND1
translocations and the genomic profile of 13 SOX11-negative aggressive B-cell lymphomas using whole genome/exome and target sequencing. The mechanism behind the translocation was an aberrant V(D)J rearrangement in three tumors and by an anomalous IGH class-switch recombination (CSR) or somatic hypermutation (SHM) mechanism in ten. The tumors with a V(D)J-mediated translocation were two blastoid MCL and one high-grade B-cell lymphoma. None of them had a mutational profile suggestive of DLBCL. The ten tumors with CSR/SHM-mediated
IGH
::
CCND1
were mainly large B-cell lymphomas, with mutated genes commonly seen in DLBCL and
BCL6
rearrangements in 6. Two cases, which transformed from marginal zone lymphomas, carried mutations in
KLF2
,
TNFAIP3
and
KMT2D
. These findings expand the spectrum of tumors carrying
CCND1
rearrangement that may occur as a secondary event in DLBCL mediated by aberrant CSR/SHM and associated with a mutational profile different from that of MCL. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2044-5385 2044-5385 |
DOI: | 10.1038/s41408-024-01146-z |