Genomic and epigenomic insights into the origin, pathogenesis and clinical behavior of mantle cell lymphoma subtypes
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PROVIDER: EGAS00001004165 | EGA |
REPOSITORIES: EGA
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Project description:In this study we compared the expression of 30215 genes in mantle cell lymphoma-initiating cells (MCL-ICs) with mantle cell lymphoma-non-initiating cells (MCL-non-ICs) and B-cells from healthy donor
2014-08-02 | GSE60023 | GEO
Project description:Mantle cell lymphoma is characterized by a t(11;14) chromosomal translocation; however, it alone is insufficient to result in the disease. A number of secondary genetic alterations have been proposed as essential in MCL pathogenesis. Amongst these, numerous copy number altered regions remain ill-defined, both for location and prognostic significance. In this study we examined in detail the genomes of a panel of 52 MCL cases. Relating gene dosage alterations to disease outcome, we found seven loci that correlated with overall survival. A survival model was constructed based on four of these loci (P = 5.87 x 10-6). Using serial analysis of gene expression and quantitative PCR we investigated the expression of genes within these altered regions and determined that CCNI and CCNG2 may be important in MCL pathogenesis (P = 0.0201 and P = 0.0292, respectively). Our findings reinforce the hypothesis that cell cycle deregulation and apoptosis are key factors in MCL pathogenesis. Array CGH, Long-SAGE, and qPCR were utilized to determine regions of the genome that have prognostic significance when altered in copy number in MCL.
2010-10-01 | E-GEOD-13331 | biostudies-arrayexpress
Project description:In this study we compared the expression of 30215 genes in mantle cell lymphoma-initiating cells (MCL-ICs) with mantle cell lymphoma-non-initiating cells (MCL-non-ICs) and B-cells from healthy donor Three samples each of MCL-ICs and MCL-non-ICs were isolated from aphresis of 3 mantle cell lymphoma primary patient samples and 2 samples of CD19+ Bcells isolated from buffy coats of healthy donor Microarray include both coding and non-coding transcripts but only mRNA coding transcript were included in this study.
2014-08-02 | E-GEOD-60023 | biostudies-arrayexpress
Project description:Mantle cell lymphoma (MCL) is a mature B-cell neoplasm initially driven by CCND1 rearrangement with 2 molecular subtypes, conventional MCL (cMCL) and leukemic non-nodal MCL (nnMCL), that differ in their clinicobiological behavior. To identify the genetic and epigenetic alterations determining this diversity, we used whole-genome (n = 61) and exome (n = 21) sequencing (74% cMCL, 26% nnMCL) combined with transcriptome and DNA methylation profiles in the context of 5 MCL reference epigenomes. We identified that open and active chromatin at the major translocation cluster locus might facilitate the t(11;14)(q13;32), which modifies the 3-dimensional structure of the involved regions. This translocation is mainly acquired in precursor B cells mediated by recombination-activating genes in both MCL subtypes, whereas in 8% of cases the translocation occurs in mature B cells mediated by activation-induced cytidine deaminase. We identified novel recurrent MCL drivers, including CDKN1B, SAMHD1, BCOR, SYNE1, HNRNPH1, SMARCB1, and DAZAP1. Complex structural alterations emerge as a relevant early oncogenic mechanism in MCL, targeting key driver genes. Breakage-fusion-bridge cycles and translocations activated oncogenes (BMI1, MIR17HG, TERT, MYC, and MYCN), generating gene amplifications and remodeling regulatory regions. cMCL carried significant higher numbers of structural variants, copy number alterations, and driver changes than nnMCL, with exclusive alterations of ATM in cMCL, whereas TP53 and TERT alterations were slightly enriched in nnMCL. Several drivers had prognostic impact, but only TP53 and MYC aberrations added value independently of genomic complexity. An increasing genomic complexity, together with the presence of breakage-fusion-bridge cycles and high DNA methylation changes related to the proliferative cell history, defines patients with different clinical evolution.
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Project description:Mantle cell lymphoma is characterized by a t(11;14) chromosomal translocation; however, it alone is insufficient to result in the disease. A number of secondary genetic alterations have been proposed as essential in MCL pathogenesis. Amongst these, numerous copy number altered regions remain ill-defined, both for location and prognostic significance. In this study we examined in detail the genomes of a panel of 52 MCL cases. Relating gene dosage alterations to disease outcome, we found seven loci that correlated with overall survival. A survival model was constructed based on four of these loci (P = 5.87 x 10-6). Using serial analysis of gene expression and quantitative PCR we investigated the expression of genes within these altered regions and determined that CCNI and CCNG2 may be important in MCL pathogenesis (P = 0.0201 and P = 0.0292, respectively). Our findings reinforce the hypothesis that cell cycle deregulation and apoptosis are key factors in MCL pathogenesis.
2009-12-01 | GSE13331 | GEO
Project description:Mantle Cell lymphoma (MCL) were treated with the BTK inhibitor 1mM CC-292 for 48h We used microarrays to uncover the mechanisms underlying CC-292 activity in Mantle Cell lymphoma (MCL)
2017-09-01 | GSE94328 | GEO
Project description:The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma Keywords: lymphochip; MCL; untreated Tumor biopsies from 71 untreated patients with mantle cell lymphoma
2010-05-23 | E-GEOD-10793 | biostudies-arrayexpress
Project description:The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma Keywords: lymphochip; MCL; untreated
2008-04-01 | GSE10793 | GEO
Project description:Mantle Cell Lymphoma (MCL) is a mostly incurable malignancy arising from naïve B cells (NBC) in the mantle zone of lymph node follicles. We analyzed genome-wide methylation in MCL patients using the HELP (Hpa II tiny fragment Enrichment by Ligation mediated PCR) assay and found significant aberrancy in promoter methylation patterns as compared to normal NBCs. Using biological and stringent statistical criteria, we further identified four hypermethylated genes CDKN2B, MLF-1, PCDH8, HOXD8 and four hypomethylated genes CD37, HDAC1, NOTCH1 and CDK5 where aberrant methylation was associated with inverse changes in mRNA levels. MassArray Epityper analysis confirmed the presence of differential methylation at the promoter region of these genes. Immunohistochemical analysis of an independent cohort of 14 MCL patient samples, confirmed CD37 surface expression in 93% of patients, validating its selection as a target for MCL therapy. Treatment of MCL cell lines with a novel small modular immunopharmaceutical(CD37-SMIP) resulted in significant loss of viability in cell lines with intense surface CD37 expression. Treatment of MCL cell lines with the DNA methyltransferase inhibitor decitabine resulted in reversal of aberrant hypermethylation and synergized with the HDAC inhibitor SAHA in induction of the four hypermethylated genes CDKN2B, MLF-1, PCDH8 and HOXD8. The combination of Decitabine and SAHA also resulted in potent and synergistic anti-MCL cytotoxicity as compared to either drug alone. In conclusion, our analysis shows prominent and aberrant methylation of the MCL genome and identifies novel differentially methylated and expressed genes in MCL cell lines and patient samples. Furthermore, our data suggest that differentially methylated genes can be targeted for therapeutic benefit in MCL. Gene expression profiling by array comprised of 8 mantle cell lymphoma (MCL) cell lines and 8 leukemic blast from blood from patients newly diagnosed with MCL. Unbiased genome-wide analysis of DNA methylation in leukemic blast from peripheral blood or pheresis products from 22 patients newly diagnosed with mantle cell lymphoma (MCL) prior to any treatment. 10 IgD+ Na ve B cells from specimens from healthy donors undergoing routine tonsillectomy were used as appropriate controls. Methylation patterns of 13 MCL cell lines were also compared.
2010-07-30 | E-GEOD-19243 | biostudies-arrayexpress
Project description:The genes regulated by SOX11 in MCL was investigated in MCL cell line Granta 519 by siRNA knock down system. Cells were transfected using the LONZA electroporation system. Results represent cells harvested after 20 hours. Details of the experiment is published in PMID 21124928. Gene expression profiles (Human Gene 1.0 ST) of mantle cell lymphoma (MCL) cell line Granta 519 treated with SOX11 siRNA. Data analyses were performed using the Affymetrix Expression Console (v. 1.1)
2010-11-29 | E-GEOD-25621 | biostudies-arrayexpress