Alternative genetic alterations of MYC, BCL2, and/or BCL6 in high‐grade B‐cell lymphoma (HGBL) and diffuse large B‐cell lymphoma (DLBCL): Can we identify different prognostic subgroups?

High‐grade B‐cell lymphoma (HGBL)/diffuse large B‐cell lymphoma (DLBCL) with rearrangements (R) in MYC and BCL2 and/or BCL6 are correlated with poor prognosis. Little is known about the impact of other genetic alterations (gain (G) or amplification (A)) of these genes. The aim of the study was to in...

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Published in:Genes chromosomes & cancer 2024-01, Vol.63 (1), p.e23211-n/a
Main Authors: Blomme, Siska, De Paepe, Pascale, Devos, Helena, Emmerechts, Jan, Snauwaert, Sylvia, Cauwelier, Barbara
Format: Article
Language:English
Subjects:
Bcl-2 protein
Bcl-6 protein
BCL2
BCL6
DLBCL
Fluorescence in situ hybridization
Gene Rearrangement
genetic alterations
HGBL
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Lymphoma
Lymphoma, Large B-Cell, Diffuse - genetics
Lymphoma, Large B-Cell, Diffuse - pathology
Medical prognosis
MYC
Myc protein
Prognosis
prognostic subgroups
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-6 - genetics
Proto-Oncogene Proteins c-myc - genetics
Retrospective Studies
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Summary:High‐grade B‐cell lymphoma (HGBL)/diffuse large B‐cell lymphoma (DLBCL) with rearrangements (R) in MYC and BCL2 and/or BCL6 are correlated with poor prognosis. Little is known about the impact of other genetic alterations (gain (G) or amplification (A)) of these genes. The aim of the study was to investigate whether we can identify new prognostic subgroups. Fluorescence in situ hybridization (FISH) results from 169 HGBL/DLBCL were retrospectively categorized into: (1) concurrent MYC‐R and BCL2‐R and/or BCL6‐R—samples with MYC‐R and BCL2‐R (+/− BCL6‐R); n = 21, and HGBL/DLBCL with MYC‐R and BCL6‐R; n = 11; (2) concurrent R and G/A in MYC and BCL2 and/or BCL6 called “alternative HGBL/DLBCL”—samples with (n = 16) or without (n = 6) BCL2 involvement; (3) BCL2 and/or BCL6 alterations without MYC involvement (n = 35); (4) concurrent G/A in MYC and BCL2 and/or BCL6 without R (n = 25); and (5) “No alterations” (n = 55). Patients with HGBL/DLBCL‐MYC/BCL2 and “alternative” HGBL/DLBCL (with BCL2 involvement) had significantly worse survival rates compared to the “no alterations” group. G/A of these genes in the absence of rearrangements did not show any prognostic significance. HGBL/DLBCL with MYC‐R and BCL6‐R without BCL2 involvement showed a better survival rate compared to HGBL/DLBCL‐MYC/BCL2. According to immunohistochemistry, “double/triple” expression (DEL/TEL) did not show a significantly worse outcome compared to absent DEL/TEL. This study highlights the continued value of FISH assessment of MYC, BCL2, and BCL6 in the initial evaluation of HGBL/DLBCL with different survival rates between several genetic subgroups.
ISSN:1045-2257
1098-2264
1098-2264
DOI:10.1002/gcc.23211