5 research outputs found
New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling
Lymphomas are assumed to originate at different stages of lymphocyte development through chromosomal aberrations. Thus, different lymphomas resemble lymphocytes at distinct differentiation stages and show characteristic morphologic, genetic, and transcriptional features. Here, we have performed a microarray-based DNA methylation profiling of 83 mature aggressive B-cell non-Hodgkin lymphomas (maB-NHLs) characterized for their morphologic, genetic, and transcriptional features, including molecular Burkitt lymphomas and diffuse large B-cell lymphomas. Hierarchic clustering indicated that methylation patterns in maB-NHLs were not strictly associated with morphologic, genetic, or transcriptional features. By supervised analyses, we identified 56 genes de novo methylated in all lymphoma subtypes studied and 22 methylated in a lymphoma subtype-specific manner. Remarkably, the group of genes de novo methylated in all lymphoma subtypes was significantly enriched for polycomb targets in embryonic stem cells. De novo methylated genes in all maB-NHLs studied were expressed at low levels in lymphomas and normal hematopoietic tissues but not in nonhematopoietic tissues. These findings, especially the enrichment for polycomb targets in stem cells, indicate that maB-NHLs with different morphologic, genetic, and transcriptional background share a similar stem cell-like epigenetic pattern. This suggests that maB-NHLs originate from cells with stem cell features or that stemness was acquired during lymphomagenesis by epigenetic remodeling
New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling
Lymphomas are assumed to originate at
different stages of lymphocyte development
through chromosomal aberrations.
Thus, different lymphomas resemble lymphocytes
at distinct differentiation stages
and show characteristic morphologic, genetic,
and transcriptional features. Here,
we have performed a microarray-based
DNA methylation profiling of 83 mature
aggressive B-cell non-Hodgkin lymphomas
(maB-NHLs) characterized for their
morphologic, genetic, and transcriptional
features, including molecular Burkitt lymphomas
and diffuse large B-cell lymphomas.
Hierarchic clustering indicated that
methylation patterns in maB-NHLs were
not strictly associated with morphologic,
genetic, or transcriptional features. By
supervised analyses, we identified
56 genes de novo methylated in all lymphoma
subtypes studied and 22 methylated
in a lymphoma subtype–specific
manner. Remarkably, the group of genes
de novo methylated in all lymphoma subtypes
was significantly enriched for polycomb
targets in embryonic stem cells. De
novo methylated genes in all maB-NHLs
studied were expressed at low levels in
lymphomas and normal hematopoietic tissues
but not in nonhematopoietic tissues.
These findings, especially the enrichment
for polycomb targets in stem
cells, indicate that maB-NHLs with different
morphologic, genetic, and transcriptional
background share a similar stem
cell–like epigenetic pattern. This suggests
that maB-NHLs originate from cells
with stem cell features or that stemness
was acquired during lymphomagenesis
by epigenetic remodeling