scholarly journals DNA repair genes are selectively mutated in diffuse large B cell lymphomas

2013 ◽  
Vol 210 (9) ◽  
pp. 1729-1742 ◽  
Author(s):  
Noel FCC de Miranda ◽  
Roujun Peng ◽  
Konstantinos Georgiou ◽  
Chenglin Wu ◽  
Elin Falk Sörqvist ◽  
...  
Keyword(s):  
Dna Repair ◽  
B Cell ◽  
Genomic Instability ◽  
Novel Mutation ◽  
B Cell Lymphoma ◽  
Germline Mutations ◽  
Dna Repair Genes ◽  
B Cell Lymphomas ◽  
Repair Genes ◽  
Large B Cell

DNA repair mechanisms are fundamental for B cell development, which relies on the somatic diversification of the immunoglobulin genes by V(D)J recombination, somatic hypermutation, and class switch recombination. Their failure is postulated to promote genomic instability and malignant transformation in B cells. By performing targeted sequencing of 73 key DNA repair genes in 29 B cell lymphoma samples, somatic and germline mutations were identified in various DNA repair pathways, mainly in diffuse large B cell lymphomas (DLBCLs). Mutations in mismatch repair genes (EXO1, MSH2, and MSH6) were associated with microsatellite instability, increased number of somatic insertions/deletions, and altered mutation signatures in tumors. Somatic mutations in nonhomologous end-joining (NHEJ) genes (DCLRE1C/ARTEMIS, PRKDC/DNA-PKcs, XRCC5/KU80, and XRCC6/KU70) were identified in four DLBCL tumors and cytogenetic analyses revealed that translocations involving the immunoglobulin-heavy chain locus occurred exclusively in NHEJ-mutated samples. The novel mutation targets, CHEK2 and PARP1, were further screened in expanded DLBCL cohorts, and somatic as well as novel and rare germline mutations were identified in 8 and 5% of analyzed tumors, respectively. By correlating defects in a subset of DNA damage response and repair genes with genomic instability events in tumors, we propose that these genes play a role in DLBCL lymphomagenesis.

ASSOCIATION BETWEEN GENETIC POLYMORPHISM IN DNA REPAIR GENES AND RISK OF B-CELL LYMPHOMA

2009 ◽  
Vol 26 (6) ◽  
pp. 467-472
Author(s):  
Safa Barıs ◽  
Tiraje Celkan ◽  
Bahadır Batar ◽  
Mehmet Guven ◽  
Mine Ozdil ◽  
...  
Keyword(s):  
Dna Repair ◽  
Genetic Polymorphism ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Dna Repair Genes ◽  
Repair Genes

ASSOCIATION BETWEEN GENETIC POLYMORPHISM IN DNA REPAIR GENES AND RISK OF B-CELL LYMPHOMA

2009 ◽  
Vol 26 (6) ◽  
pp. 467-472 ◽  
Author(s):  
Safa Barış ◽  
Tiraje Celkan ◽  
Bahadır Batar ◽  
Mehmet Güven ◽  
Mine Özdil ◽  
...  
Keyword(s):  
Dna Repair ◽  
Genetic Polymorphism ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Dna Repair Genes ◽  
Repair Genes

scholarly journals Multigene panel analysis identified germline mutations of DNA repair genes in breast and ovarian cancer

2015 ◽  
Vol 3 (5) ◽  
pp. 459-466 ◽  
Author(s):  
Yosuke Hirotsu ◽  
Hiroshi Nakagomi ◽  
Ikuko Sakamoto ◽  
Kenji Amemiya ◽  
Toshio Oyama ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Germline Mutations ◽  
Dna Repair Genes ◽  
Panel Analysis ◽  
Breast And Ovarian Cancer ◽  
Repair Genes ◽  
Multigene Panel

scholarly journals Two Cases of Diffuse Large B-Cell Lymphomas in the Cervical Lymph Nodes in Patients with Low-Grade Gastric Marginal Zone B-Cell Lymphoma (MALT Lymphoma)

2013 ◽  
Vol 46 (3) ◽  
pp. 288 ◽  
Author(s):  
Ji Hoon Jung ◽  
Hwoon-Yong Jung ◽  
Hwan Yoon ◽  
Jae Kwang Lee ◽  
Ji Hoon Kang ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
B Cell ◽  
Malt Lymphoma ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
B Cell Lymphomas ◽  
Cervical Lymph Nodes ◽  
Large B Cell

T-cell-rich B-cell lymphomas: diagnosis and response to therapy of 44 patients.

1995 ◽  
Vol 13 (7) ◽  
pp. 1742-1750 ◽  
Author(s):  
J P Greer ◽  
W R Macon ◽  
R E Lamar ◽  
S N Wolff ◽  
R S Stein ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Combination Chemotherapy ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Response To Therapy ◽  
B Cell Lymphomas ◽  
Intermediate Grade ◽  
Large B Cell

PURPOSE Clinicopathologic features of 44 patients with well-documented T-cell-rich B-cell lymphomas (TCRBCLs) were reviewed to determine if there were distinguishing clinical characteristics and to evaluate the responsiveness to therapy. PATIENTS AND METHODS Forty-one patients had de novo TCRBCL, while three patients had a prior diagnosis of diffuse large B-cell lymphoma. Seventeen TCRBCLs were identified from a retrospective analysis of 176 lymphomas diagnosed before 1988 as peripheral T-cell lymphoma (PTCLs). The initial pathologic diagnosis was incorrect in 36 of 44 cases (82%), usually due to the absence of adequate immunophenotypic and/or genotypic studies at the initial study. RESULTS The median age of patients was 53 years (range, 17 to 92), and the male-to-female ratio was 1.4:1. B symptoms were present in 22 of 41 patients (54%); splenomegaly was detected in 11 patients (25%). Clinical stage at diagnosis was as follows: I (n = 8), II (n = 6), III (n = 15), IV (n = 14), and unstaged (n = 1). Although therapy was heterogeneous, the disease-free survival (DFS) and overall survival (OS) rates at 3 years for patients with de novo TCRBCL were 29% and 46%, respectively. A complete response (CR) to combination chemotherapy for intermediate-grade lymphomas was observed in 16 of 26 patients (62%); 11 of these patients (42%) had a continuous CR, compared with one of 14 patients (7%) who received radiation therapy or therapy for low-grade lymphoma or Hodgkin's disease (HD) (P < .05). However, there was no difference in OS between patients who received chemotherapy for intermediate-grade lymphoma versus other therapies (49% v 48%) due to a high response rate to salvage therapies, including seven patients without disease after marrow transplantation. CONCLUSION TCRBCLs are difficult to recognize without immunoperoxidase studies. Patients with TCRBCL have clinical features similar to patients with other large B-cell lymphomas, except they may have more splenomegaly and advanced-stage disease; they should receive combination chemotherapy directed at large-cell lymphomas.

scholarly journals A Practical Approach to Diagnosis of B-Cell Lymphomas With Diffuse Large Cell Morphology

2020 ◽  
Vol 144 (2) ◽  
pp. 160-167
Author(s):  
Joy F. King ◽  
John T. Lam
Keyword(s):  
B Cell ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
World Health ◽  
Lymphoid Tissues ◽  
Community Practice ◽  
B Cell Lymphomas ◽  
General Pathology ◽  
Large B Cell

Context.— Large B-cell lymphomas represent the most common non-Hodgkin lymphomas and often present as extranodal masses with advanced stage similar to metastatic tumors. Without proper intraoperative, microscopic, immunophenotypic, and cytogenetic evaluation they may be mistaken for other hematopoietic or even nonhematopoietic tumors. Also, diffuse large B-cell lymphomas often have clinical, morphologic, immunophenotypic, and cytogenetic clinical features that are similar to those of other less common B-cell lymphomas. Furthermore, classification of these neoplasms is continually becoming more refined. Objective.— To provide a rational, methodic approach to the evaluation of large B-cell lymphomas for community practice pathologists who provide general pathology services. Data Sources.— This review incorporates guidelines detailed in the 2017 update to the World Health Organization's Classification of Tumours of Haematopoietic and Lymphoid Tissues in addition to other recent peer-reviewed publications. Conclusions.— Many large B-cell neoplasms respond favorably to current treatments, but these cases also require accurate and timely diagnoses. We propose a process following a brief checklist that focuses on diffuse large B-cell lymphoma, the most common entity, and rules out other similar lymphomas in a stepwise fashion.

bcl-2 protein expression in primary cutaneous large B-cell lymphoma is site-related.

1998 ◽  
Vol 16 (6) ◽  
pp. 2080-2085 ◽  
Author(s):  
F A Geelen ◽  
M H Vermeer ◽  
C J Meijer ◽  
S C Van der Putte ◽  
E Kerkhof ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
B Cell Lymphomas ◽  
European Organization ◽  
Clinical Behavior ◽  
Large B Cell Lymphoma ◽  
Cutaneous Lymphomas ◽  
Distinct Disease ◽  
Large B Cell

PURPOSE Primary cutaneous large B-cell lymphoma (PCLBCL) that presents on the leg has recently been recognized as a distinct disease entity. These lymphomas have a reduced disease-free survival and a worse prognosis as compared with the more common, morphologically similar PCLBCL that present on the head or trunk. Studies in noncutaneous diffuse large B-cell lymphomas suggest a relationship between the expression of bcl-2 protein and clinical behavior. In the present study, we investigated whether these two groups of PCLBCL differ in the expression of bcl-2 protein and the presence of t(4;18), known as one of the causes of bcl-2 overexpression. PATIENTS AND METHODS Paraffin sections from pretreatment biopsies of 14 PCLBCLs of the head or trunk and nine PCLBCLs of the legs were investigated for expression of bcl-2 protein using immunohistochemistry, and for the presence of the 14;18 translocation using polymerase chain reaction (PCR) amplification with primers against both the major breakpoint region (mbr) and the minor cluster region (mcr) of bcl-2. For reasons of comparison, nine secondary cutaneous large B-cell lymphomas (SCLBCLs) were also studied. RESULTS Expression of bcl-2 protein was found in all nine PCLBCLs of the leg and in all nine SCLBCLs, but not in any of the 14 PCLBCLs on the head and trunk. The t(14;18) was only detected in two of seven SCLBCLs, but not in the five PCLBCLs of the leg or the eight PCLBCLs on the head or trunk studied. CONCLUSION The striking differences in bcl-2 expression between PCLBCL of the head or trunk and PCLBCL on the leg suggest that bcl-2 expression is site-related and may contribute to the different clinical behavior between these two groups of lymphomas. In addition, they underscore that PCLBCL on the head and trunk and PCLBCL on the leg are distinct disease entities, as recently recognized in the European Organization for Research and Treatment of Cancer (EORTC) classification for primary cutaneous lymphomas.

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