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

Identification of Candidate Tumor Suppressor Genes Silenced Epigenetically in Mantle Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3001-3001
Author(s):  
Norihiko Kawamata ◽  
Takayuki Saitoh ◽  
Sakura Sakajiri ◽  
Phillip H. Koeffler
Keyword(s):  
Tumor Suppressor ◽  
Mantle Cell Lymphoma ◽  
Real Time ◽  
Real Time Pcr ◽  
Tumor Suppressor Genes ◽  
Cell Lymphoma ◽  
Suppressor Genes ◽  
Expression Levels ◽  
Candidate Tumor Suppressor ◽  
Mantle Cell

Abstract Many tumor suppressor genes are silenced by epigenetic mechanisms in human cancers, including mantle cell lymphoma (MCL). In this study, we have used a variety of research tools to screen for genes that are epigenetically silenced in MCL. Changes in the global gene expression profile of the MCL cell line, Jeko1, were analyzed after treatment with the combination of the demethylating agent, 5-aza-2′-deoxycytidine, and the histone deacetylase inhibitor, suberoyl anilide bishydroxamide, by DNA microarray technique. By screening over 22,000 genes, we identified 26 candidate tumor suppressor genes, expression of which were enhanced by the treatment, in the MCL line. Basal expression of these 26 genes were low in Jeko1 cells. The treatment enhanced the expression more than 2 folds and the enhancement was also confirmed by real-time PCR. Methylation status of these 26 genes were examined by bisulfite sequencing and/or combined bisulfite and restriction enzyme digestion assay in Jeko1 cells. We found hypermethylation of a CpG island in the middle of the INPP5F gene. We also found the hypermethylation of that region of INPP5F in normal peripheral blood. We also examined expression levels of these 26 genes in normal mantle cells by real-time PCR and found only 11 genes showed high levels of transcription in laser-dissected normal mantle cells. We examined expression of these 11 genes in eight MCL clinical samples by real-time PCR and found that only three genes, INPP5F, DUSP10 and FGD2 showed very low expression levels. We conclude that expression of INPP5F, DUSP10 and FGD2 genes were suppressed in MCL cells although the expression of these genes are high in normal mantle cells. INPP5F is a inositol phosphatase and could be involved in PI3K pathway. DUSP10 is a dual specific phosphatase and could be involved in JNK pathway. FGD2 is a RAS-GAP gene and could be involved in RAS pathway. These three genes may be candidate tumor suppressor genes in MCL and further functional analysis is ongoing.

Real-time Quantitative RT-PCR of Cyclin D1 mRNA in Mantle Cell Lymphoma: Comparison with FISH and Immunohistochemistry

2003 ◽  
Vol 44 (8) ◽  
pp. 1385-1394 ◽  
Author(s):  
Pei Hui* ◽  
John G. Howe* ◽  
Jill Crouch ◽  
Manjunath Nimmakayalu ◽  
Mazin B. Qumsiyeh ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Real Time ◽  
Cell Lymphoma ◽  
Rt Pcr ◽  
Mantle Cell

scholarly journals CyclinD1/CyclinD3 Ratio by Real-Time PCR Improves Specificity for the Diagnosis of Mantle Cell Lymphoma

2004 ◽  
Vol 6 (2) ◽  
pp. 84-89 ◽  
Author(s):  
Carol D. Jones ◽  
Katherine H. Darnell ◽  
Roger A. Warnke ◽  
James L. Zehnder
Keyword(s):  
Mantle Cell Lymphoma ◽  
Real Time ◽  
Real Time Pcr ◽  
Cell Lymphoma ◽  
Mantle Cell

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.

Phase II Trial of Single-Agent Temsirolimus (CCI-779) for Relapsed Mantle Cell Lymphoma

2005 ◽  
Vol 23 (23) ◽  
pp. 5347-5356 ◽  
Author(s):  
Thomas E. Witzig ◽  
Susan M. Geyer ◽  
Irene Ghobrial ◽  
David J. Inwards ◽  
Rafael Fonseca ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Messenger Rna ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Mammalian Target Of Rapamycin ◽  
Complete Response ◽  
Therapeutic Benefit ◽  
Mantle Cell ◽  
Duration Of Response

Purpose Mantle cell lymphoma (MCL) is characterized by a t(11;14) resulting in overexpression of cyclin D1 messenger RNA. This study tested whether temsirolimus (previously known as CCI-779), an inhibitor of the mammalian target of rapamycin kinase that regulates cyclin D1 translation, could produce tumor responses in patients with MCL. Patients and Methods Patients with relapsed or refractory MCL were eligible to receive temsirolimus 250 mg intravenously every week as a single agent. Patients with a tumor response after six cycles were eligible to continue drug for a total of 12 cycles or two cycles after complete remission, and were then observed without maintenance. Results Thirty-five patients were enrolled and were assessable for toxicity; one patient had MCL by histology but was cyclin D1 negative and was ineligible for efficacy. The median age was 70 years (range, 38 to 89 years), 91% were stage 4, and 69% had two or more extranodal sites. Patients had received a median of three prior therapies (range, one to 11), and 54% were refractory to the last treatment. The overall response rate was 38% (13 of 34 patients; 90% CI, 24% to 54%) with one complete response (3%) and 12 partial responses (35%). The median time-to-progression in all patients was 6.5 months (95% CI, 2.9 to 8.3 months), and the duration of response for the 13 responders was 6.9 months (95% CI, 5.2 to 12.4 months). Hematologic toxicities were the most common, with 71% (25 of 35 patients) having grade 3 and 11% (four of 35 patients) having grade 4 toxicities observed. Thrombocytopenia was the most frequent cause of dose reductions but was of short duration, typically resolving within 1 week. Conclusions Single-agent temsirolimus has substantial antitumor activity in relapsed MCL. This study demonstrates that agents that selectively target cellular pathways dysregulated in MCL cells can produce therapeutic benefit. Further studies of this agent in MCL and other lymphoid malignancies are warranted.

scholarly journals Real-Time Quantitative Reverse Transcription-PCR for Cyclin D1 mRNA in Blood, Marrow, and Tissue Specimens for Diagnosis of Mantle Cell Lymphoma

2004 ◽  
Vol 50 (1) ◽  
pp. 80-87 ◽  
Author(s):  
John Greg Howe ◽  
Jill Crouch ◽  
Dennis Cooper ◽  
Brian R Smith
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Real Time ◽  
Reverse Transcription ◽  
Cell Lymphoma ◽  
Rt Pcr ◽  
Lymphoproliferative Diseases ◽  
Β2 Microglobulin ◽  
Reverse Transcription Pcr ◽  
Mantle Cell

Abstract Background: Overexpression of cyclin D1 mRNA, found in mantle cell lymphoma (MCL), is a critical diagnostic marker. We investigated the use of real-time reverse transcription-PCR (RT-PCR) for cyclin D1. Methods: We studied 97 fresh specimens (50 blood, 30 bone marrow, 15 lymph node, and 2 other samples) from patients diagnosed with a variety of lymphoproliferative diseases, including 25 cases of MCL. We used real-time quantitative RT-PCR to evaluate cyclin D1 mRNA expression. Because blood and marrow specimens may contain only a minority of potentially malignant cells (as opposed to most lymph nodes) and to increase sensitivity, we normalized the cyclin D1 mRNA concentrations to mRNA of a B-cell-specific marker, CD19, as well as to previously characterized β2-microglobulin mRNA. Results: In 16 of 21 cases of MCL with overt disease, the ratio of cyclin D1 mRNA to β2-microglobulin mRNA was increased, but all 21 cases showed increased ratios of cyclin D1 mRNA to CD19 mRNA. Cyclin D1 mRNA was low or undetectable in various lymphoproliferative diseases, including cases of ambiguous immunophenotype. The mRNA ratios were stable over 3–7 days of sample storage. Conclusion: Quantitative RT-PCR for cyclin D1 mRNA normalized to CD19 mRNA can be used in the diagnosis of MCL in blood, marrow, and tissue.

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