Integrated CGH- and Epression Array Profiling of Mantle Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2252-2252
Author(s):  
Margit Schraders ◽  
Pedro Jares ◽  
Silvia Bea ◽  
Eric F.P.M. Schoenmakers ◽  
Joannes H.J.M. Van Krieken ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Copy Number ◽  
Array Cgh ◽  
Cell Lymphoma ◽  
Gene Dosage ◽  
Rna Expression ◽  
Array Analysis ◽  
Expression Array ◽  
Mantle Cell

Abstract Mantle cell lymphoma (MCL) is characterized by the translocation t(11;14)(q13;q32), which leads to the overexpression of cyclin D1. The cyclin D1-overexpression by itself is however not sufficient for lymphoma development. To identify other genes that are deregulated in MCL, we have performed integrated profiling of high-resolution array-based comparative genomic hybridization (array-CGH) with RNA-expression array analysis on the same set of MCL cases. DNA-alterations of MCL cases were assessed using a 3.6k BAC array with a resolution of 800 kb. On the same cases, RNA-expression array analysis was performed using the GeneChip® Human Genome U133 Plus 2.0 Array from Affymetrix. Integration of genomic-and transcription profiling data was performed using statistical tools. With array-CGH, we identified regions of chromosomal gain or loss and determined minimal common regions (mcr’s) by identifying the smallest region of overlap present in at least 36% of the cases. Integration of array-CGH and expression profiling was performed for genes located within the mcr’s and unsupervised clustering of gene-expression values within each mcr was performed. For several mcr’s, e.g. 1p22.1–31.1, 6q23.2–27 and 11q22.3–23.3, the clustering tree showed two groups, one with the chromosomal aberration and one without. Also, we observed that only a subset of genes located within a cytogenetic anomaly has a concomitant change in mRNA expression level. These genes are regulated by DNA-copy number (gene dosage). Amongst these, we identified several “hypothetical genes” and genes, which encode proteins involved in mitochondrial protein synthesis, the DNA damage repair pathway and the cAMP regulated pathway. This study shows the potential of the integrated profiling approach for identifying genes that are regulated by gene dosage (DNA-copy number). We anticipate that the genes we identified are important for MCL and it’s characteristic features like the low apoptosis rate and the chemotherapy-resistance.

RNA-Expression and Proteome Analysis Identify Complementary but Not Identical Molecular Targets in Enzastaurin-Treated Mantle Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1915-1915
Author(s):  
Marc Weinkauf ◽  
Grit Hutter ◽  
Yvonne Zimmermann ◽  
Elena Hartmann ◽  
Andreas Rosenwald ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lymphoma ◽  
Interaction Network ◽  
Proteome Analysis ◽  
Rna Expression ◽  
Array Analysis ◽  
Expression Array ◽  
2D Page ◽  
Mantle Cell ◽  
Functional Pathways

Abstract Abstract 1915 Poster Board I-938 Introduction: Protein kinase C beta (PKCbeta), a pivotal enzyme in B-cell signaling and survival, is over-expressed in most cases of mantle cell lymphoma (MCL) and results in activation of PI3K/AKT pathway. Enzastaurin, an oral serine/threonine kinase inhibitor, suppresses signaling through PKCbeta/PI3K/AKT pathways, induces apoptosis, reduces proliferation, and suppresses tumor-induced angiogenesis. Aim: To optimize the treatment options with this promising inhibitor the goal of this study was to elucidate the molecular pathways altered by Enzastaurin treatment in MCL. Methods: Four documented MCL cell lines (Granta 519, HBL-2, Jeko-1, Rec-1) were harvested after 2-8h Enzastaurin exposure at a previously defined dose of 10μM and analyzed by RNA-array and proteome analysis as previously described (2D-polyacrylamide-gel-electrophoresis (2D-PAGE); Weinkauf 2009). Regulated molecules were mapped in a functional interaction network and candidates representing different pathways were verified by Western blotting. Results: Enzastaurin exposure led to significant reduction of cell viability in all cell lines (15-20%). This was also reflected in distinct alterations of the observed protein patterns in 2D-PAGE after enzastaurin exposure. Of a total of 977 concurrent protein spots 115 (12%) spots exhibited significantly (>3fold) altered protein levels after 4h of enzastaurin exposure. Mass spectrometry of 62 protein spots (39 increase; 23 decreased) identified 108 different candidate proteins, which were used to create a protein interaction network identifying the affected functional pathways. The results of the 2D-PAGE analysis were verified by Western blot in selected candidate proteins of apoptosis (VIM, PLEC1), DNA-repair (RAD50, PCNA, RFC1) and gene expression (EEF1D, SMC1A) pathways. In parallel, RNA-expression array analysis identified 180 different genes regulated early after enzastaurin treatment. Again these genes were mapped to an interaction network, highlighting enzastaurin involvement in e.g. NFkB-, apoptosis and B-cell- and death receptor signaling pathways. Interestingly, the involved genes complemented the regulated proteins in the functional pathways. Network analysis of both screenings (2D-PAGE-based proteomics and RNA-expression array) classified the candidate molecules in functional groups, including DNA repair and replication (e.g. RAD50, PCNA), apoptosis (e.g.PSMC4, VIM), signal transduction (e.g. GRB2, EF1D) and gene expression/mRNA processing (e.g.EEF1D, SFRS7). Thus, combined analysis of both screening methods resulted in a more comprehensive network than each respective analysis. Conclusion: Enzastaurin-treatment affects three main cellular control mechanisms as highlighted by two independent screening approaches (proteomics and expression array analysis). Interestingly, these two layers of molecular response (protein and RNA respectively) resulted in minimal overlap of identified molecules at this early (4h) time, but indicated common pathways nonetheless. Ongoing experiments now incorporate this knowledge to select optimal combination partners of enzastaurin. Disclosures: Dreyling: Lilly Deutschland GmbH: Research Funding.

Cyclin D1 (CCND1) messenger RNA expression as assessed by real-time PCR contributes to diagnosis and follow-up control in patients with mantle cell lymphoma

2013 ◽  
Vol 41 (12) ◽  
pp. 1028-1037 ◽  
Author(s):  
Ulrike Bacher ◽  
Wolfgang Kern ◽  
Claudia Haferlach ◽  
Tamara Alpermann ◽  
Torsten Haferlach ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Real Time ◽  
Real Time Pcr ◽  
Messenger Rna ◽  
Cell Lymphoma ◽  
Rna Expression ◽  
Mantle Cell

scholarly journals A147 PRIMARY COLONIC MANTLE CELL LYMPHOMA: A RARE ENTITY

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 138-140
Author(s):  
K Donaldson ◽  
S Nassiri ◽  
D Chahal ◽  
M F Byrne
Keyword(s):  
Case Report ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Transverse Colon ◽  
Cell Lymphoma ◽  
Rapid Progression ◽  
Rare Entity ◽  
Gi Bleeding ◽  
Gi Tract ◽  
Mantle Cell

Abstract Background Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL), often diagnosed at later stages with secondary gastrointestinal (GI) involvement. Primary GI MCL is rare and is not often discussed in the literature. Aims To increase awareness of a rare condition that is likely to be encountered but can be challenging to diagnose. Methods Case report and review of the literature. Results Case Report A 78-year-old man with multiple untreated vascular risk factors including atrial fibrillation and type 2 diabetes presented with acute onset left hemiplegia, dysarthria, and imaging consistent with a left pontine stroke. As part of his workup he underwent a CT abdomen/pelvis identifying an 11 x 5 cm intraluminal mass in the transverse colon. Previous screening colonoscopies, for family history of colon cancer, were notable for tubular adenomas without high-grade dysplasia at 13, 12, 10, 7, and 2 years prior to admission. The patient had 16 pounds of weight loss without other constitutional symptoms, change in bowel habits or evidence of GI bleeding. Bloodwork was notable for microcytic anemia (Hemoglobin 91 g/L, MCV 75 fL), from a normal baseline one year prior, without other cytopenias. C-reactive protein (44 mg/L) and GGT (164 U/L) were elevated. Other liver enzymes, lactate dehydrogenase, and electrolytes were normal. Colonoscopy revealed numerous polypoid lesions throughout the entire colon and a large non-obstructive mass with submucosal appearance in the transverse colon. Biopsies were taken from the large mass and one of the smaller polypoid lesions. Histology showed a sheet-like infiltrate of small lymphocytes within the lamina propria. Immunohistochemical staining was positive for CD20, BCL2, Cyclin D1, equivocal for CD5, and negative for BCL6 and CD3. Ki67 index approached 30%. A diagnosis of colonic MCL was made. Literature Review Primary MCL of the GI tract is rare, accounting for only 1 to 4% of all GI malignancies. There is a male and Caucasian predominance with a median age of 68 years at diagnosis. Presenting complaints may include abdominal pain, anorexia, and GI bleeding. Typical endoscopic features are small nodular or polypoid tumors, between 2mm and 2 cm in size, along one or more segments of the GI tract referred to as multiple lymphomatous polyposis (MLP). A single colonic mass is infrequently seen, highlighting the importance of endoscopy for diagnosis, as subtle findings may be missed on radiographic evaluation. Biopsies for immunohistochemistry are essential to distinguish MCL from other NHLs, as almost all cases express cyclin D1. Despite aggressive immunochemotherapy, prognosis is often poor due to MCL’s rapid progression and early relapse. Conclusions Primary GI MCL is a rare entity. Awareness is essential as evaluation and management differ from lymphoma at other sites, and other GI malignancies. Funding Agencies None

Cyclin D1 as an Aid in the Diagnosis of Mantle Cell Lymphoma in Skin Biopsies: A Case Report

2001 ◽  
Vol 23 (5) ◽  
pp. 470-476 ◽  
Author(s):  
Brent R. Moody ◽  
Nancy L. Bartlett ◽  
David W. George ◽  
Caroline R. Price ◽  
Wayne A. Breer ◽  
...  
Keyword(s):  
Case Report ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Mantle Cell ◽  
Skin Biopsies

Antitumoral Activity of Lenalidomide in In Vitro and In Vivo Models of Mantle Cell Lymphoma Involves the Destabilization of Cyclin D1/p27KIP1 Complexes

2013 ◽  
Vol 20 (2) ◽  
pp. 393-403 ◽  
Author(s):  
Alexandra Moros ◽  
Sophie Bustany ◽  
Julie Cahu ◽  
Ifigènia Saborit-Villarroya ◽  
Antonio Martínez ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Antitumoral Activity ◽  
In Vivo Models ◽  
Mantle Cell

scholarly journals Dysregulation of cyclin D1 by translocation into an IgH gamma switch region in two multiple myeloma cell lines [see comments]

Blood ◽  
1996 ◽  
Vol 88 (2) ◽  
pp. 674-681 ◽  
Author(s):  
M Chesi ◽  
PL Bergsagel ◽  
LA Brents ◽  
CM Smith ◽  
DS Gerhard ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Myeloma Cell ◽  
Switch Region ◽  
Chromosomal Locus ◽  
Multiple Myeloma Cell ◽  
Mantle Cell ◽  
Switch Regions

Translocations involving the IgH locus at chromosomal locus 14q32.3 are a common event in many B-cell malignancies. The translocations, which generally occur into JH and switch regions, are mediated by errors in the two developmentally regulated, lymphocyte-specific pathways: VDJ- and switch-mediated recombination. Dysregulation of cyclin D1 by a t(11;14)(q13;q32) translocation occurs in most cases of mantle-cell lymphoma and in approximately 30% of multiple myeloma (MM) tumors in which a 14q32 translocation can be detected. We show here that in two of three myeloma lines that overexpress cyclin D1, there is an 11;14 translocation into a gamma switch region, suggesting an error in switch recombination. By contrast, 11;14 translocations in mantlecell lymphoma are invariably into or near a JH segment, suggesting an error in VDJ recombination. This is consistent with the fact that myeloma cells have undergone lgH switch recombination, whereas mantle-cell lymphoma cells generally have not.

scholarly journals Immunohistochemical Analysis of Cyclin D1 Protein in Hematopoietic Neoplasms with Special Reference to Mantle Cell Lymphoma

1994 ◽  
Vol 85 (12) ◽  
pp. 1270-1279 ◽  
Author(s):  
Shigeo Nakamura ◽  
Masao Seto ◽  
Shogo Banno ◽  
Susumu Suzuki ◽  
Takashi Koshikawa ◽  
...  
Keyword(s):  
Special Reference ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
D1 Protein ◽  
Immunohistochemical Analysis ◽  
Cyclin D1 Protein ◽  
Mantle Cell

Complex analysis of cyclin D1 expression in mantle cell lymphoma: two cyclin D1-negative cases detected

2009 ◽  
Vol 62 (10) ◽  
pp. 948-950 ◽  
Author(s):  
L Stefancikova ◽  
M Moulis ◽  
P Fabian ◽  
I Falkova ◽  
I Vasova ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Complex Analysis ◽  
Cell Lymphoma ◽  
In Situ Hybridisation ◽  
D1 Protein ◽  
Fluorescence In Situ Hybridisation ◽  
Cyclin D2 ◽  
Mantle Cell ◽  
High Level

Background and Aim:The cytogenetic and diagnostic hallmark of mantle cell lymphoma (MCL) is translocation t(11;14)(q13;q32), resulting in overexpression of cyclin D1. Cyclin D1 expression was analysed in 32 cases of MCL.Methods:The t(11;14) translocation was detected by fluorescence in situ hybridisation, level of cyclin D1 mRNA by competitive RT-PCR, and level of cyclin D1 and D2 proteins by immunohistochemistry and/or immunoblotting.Results:In 30 cases, the presence of translocation t(11;14), a high level of cyclin D1 mRNA, and a high level of the cyclin D1 protein were confirmed. Two cyclin D1-negative cases overexpressing cyclin D2 were detected by immunoblotting.Conclusions:There are rare cyclin D1-negative cases of MCL overexpressing cyclin D2. Anti-cyclin D1 antibodies with low specificity can bind both cyclin D1 and cyclin D2, thus providing false cyclin D1-positive signals in immunohistochemical analysis.

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