Abstract
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of diseases that have diverse clinical, pathological, and biological features. Here, it is shown that primary nodal and extranodal DLBCLs differ genomically and phenotypically. Using conventional comparative genomic hybridization (CGH), the authors assessed the chromosomal aberrations in 18 nodal, 13 extranodal, and 5 mixed DLBCLs. The results demonstrate significantly distinct chromosomal aberrations exemplified by gains of chromosomal arms 1p, 7p, 12q24.21-12q24.31, and 22q and chromosome X and loss of chromosome 4, 6q, and 18q22.3-23 in extranodal compared with nodal DLBCLs. Nodal DLBCLs showed an increased tendency for 18q amplification and BCL2 protein overexpression compared with extranodal and mixed tumors. Using a panel of five antibodies against GCET1, MUM1, CD10, BCL6, and FOXP1 proteins to subclassify DLBCLs according to the recent Choi algorithm, the authors showed that the genomic profiles observed between the nodal and extranodal DLBCLs were not due to the different proportions of GCB vs ABC in the two groups. Further delineation of these genomic differences was illuminated by the use of high-resolution 21K BAC array CGH performed on 12 independent new cases of extranodal DLBCL. The authors demonstrated for the first time a novel genome and proteome-based signatures that may differentiate the two lymphoma types.
Highlights
Non-Hodgkin’s lymphoma (NHL) is a heterogeneous group of diseases that have different morphological, immunological, cytogenetic, and molecular features
Diffuse large B-cell lymphoma (DLBCL) is the largest category of aggressive lymphoma and is regarded by many pathologists and oncologists to be a heterogeneous group of disorders that requires further subclassification
Because BCL2 gene resides on chromosome 18q, we examined BCL2 gene amplification more closely using Fluorescence In Situ Hybridization (FISH) and correlated its amplification with the CGHcopy number and BCL2 protein expression data
Summary
Non-Hodgkin’s lymphoma (NHL) is a heterogeneous group of diseases that have different morphological, immunological, cytogenetic, and molecular features. Recent statistical data from Kuwait indicate that DLBCL is the most common form of NHL. It is the third most common malignant disease among Kuwaiti women after cancer of the breast and lungs and the fifth most common among Kuwaiti men (Ameen et al 2010). DLBCL is the largest category of aggressive lymphoma and is regarded by many pathologists and oncologists to be a heterogeneous group of disorders that requires further subclassification. This view was based on the fact that morphological and immunophenotypic approaches to the diagnosis of this disease are insufficient to predict
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