Molecular Profiling of Aggressive Lymphomas (original) (raw)
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MicroRNA signatures in B-cell lymphomas
2012
Accurate lymphoma diagnosis, prognosis and therapy still require additional markers. We explore the potential relevance of microRNA (miRNA) expression in a large series that included all major B-cell non-Hodgkin lymphoma (NHL) types. The data generated were also used to identify miRNAs differentially expressed in Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) samples. A series of 147 NHL samples and 15 controls were hybridized on a human miRNA one-color platform containing probes for 470 human miRNAs. Each lymphoma type was compared against the entire set of NHLs. BL was also directly compared with DLBCL, and 43 preselected miRNAs were analyzed in a new series of routinely processed samples of 28 BLs and 43 DLBCLs using quantitative reverse transcription-polymerase chain reaction. A signature of 128 miRNAs enabled the characterization of lymphoma neoplasms, reflecting the lymphoma type, cell of origin and/or discrete oncogene alterations. Comparative analysis of BL and DLBCL yielded 19 differentially expressed miRNAs, which were confirmed in a second confirmation series of 71 paraffin-embedded samples. The set of differentially expressed miRNAs found here expands the range of potential diagnostic markers for lymphoma diagnosis, especially when differential diagnosis of BL and DLBCL is required.
Blood, 2004
Diffuse large B-cell lymphoma (DLBCL) can be divided into prognostically important subgroups with germinal center Bcell-like (GCB), activated B-cell-like (ABC), and type 3 gene expression profiles using a cDNA microarray. Tissue microarray (TMA) blocks were created from 152 cases of DLBCL, 142 of which had been successfully evaluated by cDNA microarray (75 GCB, 41 ABC, and 26 type 3). Sections were stained with antibodies to CD10, bcl-6, MUM1, FOXP1, cyclin D2, and bcl-2. Expression of bcl-6 (P < .001) or CD10 (P ؍ .019) was associated with better overall survival (OS), whereas expression of MUM1 (P ؍ .009) or cyclin D2 (P < .001) was associated with worse OS. Cases were subclassified using CD10, bcl-6, and MUM1 expression, and 64 cases (42%) were considered GCB and 88 cases (58%) non-GCB. The 5-year OS for the GCB group was 76% compared with only 34% for the non-GCB group (P < .001), which is similar to that reported using the cDNA microarray. Bcl-2 and cyclin D2 were adverse predictors in the non-GCB group. In multivariate analysis, a high International Prognostic Index score (3-5) and the non-GCB phenotype were independent adverse predictors (P < .0001). In summary, immunostains can be used to determine the GCB and non-GCB subtypes of DLBCL and predict survival similar to the cDNA microarray. (Blood. 2004;103:275-282)
Journal of Hematology & Oncology, 2012
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin Lymphoma comprising of greater than 30% of adult non-Hodgkin Lymphomas. DLBCL represents a diverse set of lymphomas, defined as diffuse proliferation of large B lymphoid cells. Numerous cytogenetic studies including karyotypes and fluorescent in situ hybridization (FISH), as well as morphological, biological, clinical, microarray and sequencing technologies have attempted to categorize DLBCL into morphological variants, molecular and immunophenotypic subgroups, as well as distinct disease entities. Despite such efforts, most lymphoma remains undistinguishable and falls into DLBCL, not otherwise specified (DLBCL-NOS). The advent of microarray-based studies (chromosome, RNA, gene expression, etc) has provided a plethora of high-resolution data that could potentially facilitate the finer classification of DLBCL. This review covers the microarray data currently published for DLBCL. We will focus on these types of data; 1) array based CGH; 2) classical CGH; and 3) gene expression profiling studies. The aims of this review were threefold: (1) to catalog chromosome loci that are present in at least 20% or more of distinct DLBCL subtypes; a detailed list of gains and losses for different subtypes was generated in a table form to illustrate specific chromosome loci affected in selected subtypes; (2) to determine common and distinct copy number alterations among the different subtypes and based on this information, characteristic and similar chromosome loci for the different subtypes were depicted in two separate chromosome ideograms; and, (3) to list reclassified subtypes and those that remained indistinguishable after review of the microarray data. To the best of our knowledge, this is the first effort to compile and review available literatures on microarray analysis data and their practical utility in classifying DLBCL subtypes. Although conventional cytogenetic methods such as Karyotypes and FISH have played a major role in classification schemes of lymphomas, better classification models are clearly needed to further understanding the biology, disease outcome and therapeutic management of DLBCL. In summary, microarray data reviewed here can provide better subtype specific classifications models for DLBCL.
PloS one, 2014
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 markers derived from the gene expression profiling-defined cell origin signature, including MYC, BCL2, BCL6, and FOXP1 protein expression. We also investigated genetic alterations in BCL2, BCL6, MYC and FOXP1 using fluorescence in situ hybridization and assessed their prognostic significance. BCL6 rearrangements were detected in 29% of cases, and BCL6 gene alteration (rearrangement and/or amplification) was associated with the non-germinal center B subtype (non-GCB). BCL2 translocation was associated with the GCB phenotype, and BCL2 protein expression was associated with the translocation and/or amplification of 18q21. MYC rearrangements were detected in 15% of cases, and MYC protein expression was observed in 29% of cases. FOXP1 expression, mainly of the non-GCB subtype, was demonstrate...
Molecular pathology of lymphoma
Eye, 2013
Ocular lymphomas can be divided into intraocular lymphomas and ocular adnexal lymphomas. The vitreoretinal lymphomausually a diffuse large B-cell lymphoma (DLBCL) of high-grade malignancy-is the most common lymphoid malignancy arising in the eye, while the extranodal marginal zone B-cell lymphoma (EMZL), an indolent often recurrent tumour, occurs most frequently in the ocular adnexal tissue. The two lymphoma subtypes differ significantly in their clinical presentation, subsequent course and outcome as well as in their underlying morphological, immunophenotypical and genetic features. The molecular processes involved in DLBCL and EMZL development are complex, and include chromosomal translocations, mutations caused by aberrant somatic hypermutation, sporadic somatic mutations, and copy number alterations, characterized by deletions and amplifications. These lead to alterations in particular signalling pathways, which in turn activate transcription factors, such as nuclear factor NF-kB. This review provides an overview of the histological features of DLBCL and EMZL, and discusses the current insights into the molecular mechanisms underlying the development of these tumours, when they occur systemically and particularly when they arise in ocular tissues. Updates in the molecular pathology of DLBCL and EMZL SE Coupland 2 Eye Updates in the molecular pathology of DLBCL and EMZL SE Coupland 8 Eye Updates in the molecular pathology of DLBCL and EMZL SE Coupland 9
The pathologist's view point. Part II --aggressive lymphomas
Haematologica, 2000
The REAL/WHO classification constitutes a new tool for the better understanding and treatment of malignant lymphomas. The authors focus on the key features of aggressive B- and T-cell lymphomas, aiming to contribute to the cross-talk between pathologists and clinicians. Each lymphoma entity is analyzed on the basis of the most representative contributions in the literature and the authors' experience gained in studying more than 20,000 lymphoid tumors over a 20-year period. Guidelines for diagnosis and areas of interest for future clinico-pathologic studies are identified and discussed. Within this context, selected data obtained by the application of novel markers are presented. The present know- ledge and organization of malignant lymphomas now make the development of tailored therapies a feasible goal.
1988
Eight reactive lymphatic tissues, 166 cases of non-Hodgkin sizes. Overall, results of Northern blotting were in good agreelymphomas (NHL) and I I cases of multiple myeloma were ment with data obtained by immunohistological methods. The investigated for expression of the c-abl protein using the poly-amount and size of abl-mRNA transcripts pointed to the conclonal anti-abl antibody 441 I and an indirect peroxidase tech-stitutive expression of c-abl predominantly in certain subtypes nique. In selected cases the results were compared to those and clinical stages of the various NHL. obtained with a second polyclonal and 2 monoclonal anti-abl antibodies. In 7 cases, Northern blot analysis of abCmRNA was performed in parallel. In reactive lymphatic tissues, cells positive for the 4411 antibody were confined to the 6-cell areas, Le., to the mantle zone and parts of the germinal Patients center. In NHL, a positive staining of the cell membrane was