BCL2 mutations in diffuse large B-cell lymphoma.
BCL2 is deregulated in diffuse large B-cell lymphoma (DLBCL) by the t(14;18) translocation, gene amplification and/or nuclear factor-κB signaling. RNA-seq data have recently shown that BCL2 is the most highly mutated gene in germinal center B-cell (GCB) DLBCL. We have sequenced BCL2 in 298 primary DLBCL biopsies, 131 additional non-Hodgkin lymphoma biopsies, 24 DLBCL cell lines and 51 germline DNAs. We found frequent BCL2 mutations in follicular lymphoma (FL) and GCB DLBCL, but low levels of BCL2 mutations in activated B-cell DLBCL, mantle cell lymphoma, small lymphocytic leukemia and peripheral T-cell lymphoma. We found no BCL2 mutations in GC centroblasts. Many mutations were non-synonymous; they were preferentially located in the flexible loop domain, with few in BCL2-homology domains. An elevated transition/transversions ratio supports that the mutations result from somatic hypermutation. BCL2 translocations correlate with, and are likely important in acquisition of, additional BCL2 mutations in GCB DLBCL and FL. DLBCL mutations were not independently associated with survival. Although previous studies of BCL2 mutations in FL have reported mutations to result in pseudo-negative BCL2 protein expression, we find this rare in de-novo DLBCL.Leukemia accepted article preview online, 22 December 2011; doi:10.1038/leu.2011.378.
Canada's Michael Smith Genome Sciences Center, BC Cancer Agency, Vancouver, British Columbia, Canada.
This article was published in the following journal.
Name: Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22189900
- DOI: http://dx.doi.org/10.1038/leu.2011.378
Context .- Diffuse large B-cell lymphoma and chronic lymphocytic leukemia are 2 of the most common B-cell lymphomas in adults. Both diffuse large B-cell lymphoma and chronic lymphocytic leukemia share...
Diffuse large B-cell lymphoma, the most common type of lymphoma in Western countries, remains incurable in approximately 40% of patients. Over the past decade, nascent molecular technologies have led ...
B-cell lymphoma of the paranasal sinuses is rare. We present the case of a 42-year-old woman who presented with proptosis, diplopia, and vision disturbances in the right eye. She was diagnosed with di...
Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. We analyzed 100 cases of DLBCL to evaluate the prognostic value of immunohistochemical m...
Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma, accounting for nearly 50% of the cases in the Hematology Department of the Hospital das Clínicas da Faculdade de Medicin...
The primary objective of the study is to evaluate the efficacy of ASCT as consolidation in case of bcl-2 overexpression in non previously treated patients aged 60 years or less with low-in...
This phase II multi-institutional trial will explore the safety and efficacy of lenalidomide monotherapy given as maintenance therapy following salvage chemo-immunotherapy in patients with...
Objectives: 1. To evaluate the safety of lenalidomide in combination with rituximab in patients with relapsed/refractory mantle cell lymphoma (MCL) and diffuse large B-cell non-hod...
This study is a multicentric trial evaluating the efficacy of R-ACVBP in patients aged 18 to 59 years with high risk diffuse large B-cell lymphoma
The purpose of this study is to obtain safety and efficacy data using tositumomab or Bexxar in patients with relapsed/refractory diffuse large cell Non-Hodgkin's lymphoma (DLCL).
Medical and Biotech [MESH] Definitions
B-cell lymphoid tumors that occur in association with AIDS. Patients often present with an advanced stage of disease and highly malignant subtypes including BURKITT LYMPHOMA; IMMUNOBLASTIC LARGE-CELL LYMPHOMA; PRIMARY EFFUSION LYMPHOMA; and DIFFUSE, LARGE B-CELL, LYMPHOMA. The tumors are often disseminated in unusual extranodal sites and chromosomal abnormalities are frequently present. It is likely that polyclonal B-cell lymphoproliferation in AIDS is a complex result of EBV infection, HIV antigenic stimulation, and T-cell-dependent HIV activation.
Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation.
A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.
A systemic, large-cell, non-Hodgkin, malignant lymphoma characterized by cells with pleomorphic appearance and expressing the CD30 ANTIGEN. These so-called "hallmark" cells have lobulated and indented nuclei. This lymphoma is often mistaken for metastatic carcinoma and MALIGNANT HISTIOCYTOSIS.
A group of malignant lymphomas thought to derive from peripheral T-lymphocytes in lymph nodes and other nonlymphoid sites. They include a broad spectrum of lymphocyte morphology, but in all instances express T-cell markers admixed with epithelioid histiocytes, plasma cells, and eosinophils. Although markedly similar to large-cell immunoblastic lymphoma (LYMPHOMA, LARGE-CELL, IMMUNOBLASTIC), this group's unique features warrant separate treatment.