Posttransplant molecular Burkitt lymphomas are frequently MYC-negative and characterized by the 11q-gain/loss pattern (original) (raw)
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Cancer Genetics, 2020
Burkitt-like lymphoma with 11q aberration" is a new provisional entity in the latest revision of lymphoma's World Health Organization classification described as carrying the specific 11q-gain/loss aberration and lacking MYC rearrangement. Morphologically, phenotypically and by gene and microRNA expression profiling these lymphomas resemble Burkitt lymphoma. The 11q-gain/loss was also found in post-transplant patients with molecular Burkitt lymphoma signature without MYC rearrangement. Recent reports describe aggressive lymphomas with coexistence of 11q-gain/loss and MYC rearrangement. In this report we describe post-transplant Burkitt-like lymphoma with 11q aberration and MYC amplification. Genetic studies were conducted at two time points: before therapy and during progression. In both cytogenetic examinations, peculiar 11q-gain/loss was detected. Percentage of cells carrying MYC amplification increased from 2% at initial diagnosis to 97% during progression. The MYC amplification can functionally correspond to MYC translocation and to MYC overexpression. The presence of MYC amplification seems to increase the aggressiveness of the reported disease course, so even a small clone with this change should be indicated in cytogenetic result.
2014
• A subset of lymphomas with gene expression and pathological characteristics of Burkitt lymphomas but absence of MYC translocation does exist. • These lymphomas carry chr 11q proximal gains and telomeric losses, suggesting co-deregulation of oncogenes and tumor suppressor genes. The genetic hallmark of Burkitt lymphoma (BL) is the t(8;14)(q24;q32) and its variants leading to activation of the MYC oncogene. It is a matter of debate whether true BL without MYC translocation exists. Here, we identified 59 lymphomas concordantly called BL by 2 gene expression classifiers among 753 B-cell lymphomas. Only 2 (3%) of these 59 molecular BL lacked a MYC translocation, which both shared a peculiar pattern of chromosome 11q aberration characterized by interstitial gains including 11q23.2-q23.3 and telomeric losses of 11q24.1-qter. We extended our analysis to 17 MYC-negative high-grade B-cell lymphomas with a similar 11q aberration and showed this aberration to be recurrently associated with morphologic and clinical features of BL. The minimal region of gain was defined by highlevel amplifications in 11q23.3 and associated with overexpression of genes including PAFAH1B2 on a transcriptional and protein level. The recurrent region of loss contained a focal homozygous deletion in 11q24.2-q24.3 including the ETS1 gene, which was shown to be mutated in 4 of 16 investigated cases. These findings indicate the existence of a molecularly distinct subset of B-cell lymphomas reminiscent of BL, which is characterized by deregulation of genes in 11q.
Molecular genetic analysis of lymphoid tumors after organ transplant
American Journal Of Pathology
A variety ofgene analyses were performed on lymphoid tumors from transplant patients who received cyclosporine A for immunosuppression. Epstein-Barr virus DNA was detected in the tumors, and the structure of circular episomal virus DNA was used as a measure ofcell clonality. This analysis was correlated with clonality determined by study of immunoglobulin gene rearrangement. Some ofthe tumors had DNA rearrangements near the c-myc gene. Analysis suggested thepathogenesis ofthe tumors and indicatedfour categories oflymphoproliferation, three neoplastic and one reactive. (AmJPathol 1989, 135:977-987) Tumors of B lymphocytes commonly arise in immunosuppressed patients.1-7 These '"post-transplant lymphoproliferations" (PTLs) range from benign hyperplasias to malignant lymphomas, and are closely associated with Epstein-Barr viral (EBV) infection.2'4'7'813 PTLs differ in clinical behavior, but it is difficult to discriminate morphologically hyperplastic from malignant lesions.27 Some tumors consist of a monomorphic cell population whereas others contain "polymorphic" maturing B cell populations, ranging from large cells to plasmacytoid cells. The morphology of the latter may resemble hyperplasia. Conversely, both monomorphic and polymorphic malignant tumors probably arise in hyperplasias. Many patients have multiple tumors in different locations. These could represent multiple neoplastic transformations, metastatic spread, or hyperplasia that is incorrectly called neoplasia.
MOLECULAR HISTOGENESIS OF POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS
2003
disorders Molecular histogenesis of posttransplantation lymphoproliferative http://bloodjournal.hematologylibrary.org/content/102/10/3775.full.html Updated information and services can be found at: (795 articles) Oncogenes and Tumor Suppressors (1643 articles) Transplantation (4217 articles) Neoplasia (4494 articles) Immunobiology Articles on similar topics can be found in the following Blood collections http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub\_requests Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#reprints Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/site/subscriptions/index.xhtml Information about subscriptions and ASH membership may be found online at: Posttransplantation lymphoproliferative disorders (PTLDs) represent a serious complication of solid organ transplantation. This study assessed the molecular histogenesis of 52 B-cell monoclonal PTLDs, including 12 polymorphic PTLDs (P-PTLDs), 36 diffuse large B-cell lymphomas (DLBCLs), and 4 Burkitt/Burkitt-like lymphomas (BL/BLLs). Somatic hypermutation (SHM) of immunoglobulin variable (IgV) genes documented that most monoclonal B-cell PTLDs (75% P-PTLDs, 91.3% DLBCLs, 100% BL/BLLs) derive from germinal center (GC)-experienced B cells. B-cell lymphoma 6 (BCL6) mutations oc-curred in 25% P-PTLDs, 60.6% DLBCLs, and 75.0% BL/BLLs. A first histogenetic category of PTLDs (31.2% DLBCLs) express the BCL6 ؉ /multiple myeloma oncogene-1 protein (MUM1 ؊/؉ )/CD138 ؊ profile and mimic B cells experiencing the GC reaction, as also suggested by ongoing SHM in a fraction of these cases. A second subset of PTLDs (66.7% P-PTLDs and 31.2% DLBCLs) display the BCL6 ؊ /MUM1 ؉ /CD138 ؊ phenotype and mimic B cells that have concluded the GC reaction. A third histogenetic category of PTLDs (25.0% P-PTLDs and 31.2% DLBCLs) shows the BCL6 ؊ / MUM1 ؉ /CD138 ؉ profile, consistent with pre-terminally differentiated post-GC B cells. Crippling mutations of IgV heavy chain (IgV H ) and/or IgV light chain (IgV L ) genes, leading to sterile rearrangements and normally preventing cell survival, occur in 4 DLBCLs and 1 BL/BLL that may have been rescued from apoptosis through expression of Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1). Overall, the histogenetic diversity of monoclonal B-cell PTLDs may help define biologically homogeneous categories of the disease. (Blood. 2003;102: 3775-3785)
Hematological Oncology, 2008
B-cell post-transplant lymphoproliferative disorders (PTLD) are classified as early lesions, polymorphic lymphomas (P-PTLD) and monomorphic lymphomas (M-PTLD). These morphologic categories are thought to reflect a biologic continuum, although supporting genetic data are lacking. To gain better insights into PTLD pathogenesis, we characterized the phenotypes, immunoglobulin (Ig) gene alterations and non-Ig gene (BCL6, RhoH/TTF, c-MYC, PAX5, CIITA, BCL7A, PIM1) mutations of 21 PTLD, including an IM-like lesion, 8 P-PTLD and 12 M-PTLD. Gene expression profile analysis was also performed in 12 cases. All PTLD with clonal Ig rearrangements showed evidence of germinal centre (GC) transit based on the analysis of Ig and BCL6 gene mutations, and 74% had a non-GC phenotype (BCL6 AE MUM1þ). Although surface Ig abnormalities were seen in 6/19 (32%) PTLD, only three showed 'crippling' Ig mutations indicating other etiologies for loss of the B-cell receptor. Aberrant somatic hypermutation (ASHM) was almost exclusively observed in M-PTLD (8/12 vs. 1/8 P-PTLD) and all three recurrent cases analysed showed additional mutations in genes targeted by ASHM. Gene expression analysis showed distinct clustering of PTLD compared to B-cell non-Hodgkin lymphomas (B-NHL) without segregation of P-PTLD from non-GC M-PTLD or EBVþ from EBVÀ PTLD. The gene expression pattern of PTLD appeared more related to that of memory and activated B-cells. Together, our results suggest that PTLD represent a distinct type of B-NHL deriving from an antigen experienced B-cell, whose evolution is associated with accrual of genetic lesions.
Modern Pathology, 2002
Numerical chromosomal imbalances were characterized by comparative genomic hybridization (CGH) performed on 54 DLBCL tumors from a total of 40 patients. The clonal relatedness was demonstrated in 9 of 11 pairs of matched diagnostic tumors and their relapses as determined by IGH gene rearrangement analysis and/or the CGH profiles. Furthermore, immunohistochemical expression analyses of BCL2 and BCL6/LAZ3 were performed on all cases. Copy number changes were detected in 94% of the diagnostic tumor samples and in all of the relapses. Chromosomal losses in diagnostic tumors were preferentially observed at 8p22-pter (29%), 1p34-pter (26%), 6q23-qter (20%), 17p12pter (17%) and 22q (17%), 9p23-pter (14%), whereas gains were mainly seen in Xq25-26 (43%), 13q22 (26%), 12cen-q14 (20%), 3q24 -25 (11%), 7 (11%), and 18q12-21 (11%). Loss of 22q was significantly more commonly seen in the diagnostic tumor samples with more advanced clinical stage in other words, Stage III-IV compared with Stage I-II, and band 18q21 was significantly more often gained in relapses as compared to diagnostic tumors. None of the recurrent alterations were detected as a single abnormality, suggesting that other genetic lesions below the detection level of CGH may be the initiating event in the tumorigenesis of DLBCL. However, the distribution of CGH alterations support the idea of a progression of genetic events where loss of 8p and 9p and gain of 3q, 13q, and 18q would represent relatively early events because they were distributed in tumors with only two abnormalities.
2014
The WHO classification of lymphomas allows for a group of diseases that have features intermediate between those of Burkitt lymphoma and diffuse large B-cell lymphoma. These are a diverse group of diseases whose genetics and clinical course are yet to be fully described. We report an unusual case of high grade B-cell lymphoma, intermediate between DLBCL and BL, lacking CD10 expression in which the chromosomal translocation t(3;8)(q27;q24) was found to be the sole chromosomal abnormality. FISH analysis demonstrated juxtaposition of the BCL6 and MYC loci without obvious involvement of the IGH locus, suggesting constitutive MYC expression due to promoter substitution. The patient responded to intensive chemotherapy and remains in remission two years after finishing therapy.