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Article ; Online: MicroRNA expression profiling using microarrays.

Love, Cassandra / Dave, Sandeep

Methods in molecular biology (Clifton, N.J.)

2013 Volume 999, Page(s) 285–296

Abstract: MicroRNAs are small noncoding RNAs which are able to regulate gene expression at both the transcriptional and translational levels. There is a growing recognition of the role of microRNAs in nearly every tissue type and cellular process. Thus there is an ...

Abstract	MicroRNAs are small noncoding RNAs which are able to regulate gene expression at both the transcriptional and translational levels. There is a growing recognition of the role of microRNAs in nearly every tissue type and cellular process. Thus there is an increasing need for accurate quantitation of microRNA expression in a variety of tissues. Microarrays provide a robust method for the examination of microRNA expression. In this chapter, we describe detailed methods for the use of microarrays to measure microRNA expression and discuss methods for the analysis of microRNA expression data.
MeSH term(s)	Gene Expression Profiling ; Humans ; MicroRNAs/genetics ; MicroRNAs/isolation & purification ; Microarray Analysis/methods
Chemical Substances	MicroRNAs
Language	English
Publishing date	2013
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-62703-357-2_21
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Article: Id Proteins Suppress E2A-Driven Invariant Natural Killer T Cell Development prior to TCR Selection.

Roy, Sumedha / Moore, Amanda J / Love, Cassandra / Reddy, Anupama / Rajagopalan, Deepthi / Dave, Sandeep S / Li, Leping / Murre, Cornelis / Zhuang, Yuan

Frontiers in immunology

2018 Volume 9, Page(s) 42

Abstract: A family of transcription factors known as E proteins, and their antagonists, Id proteins, regulate T cell differentiation at critical developmental checkpoints. Id proteins promote the differentiation of conventional αβ T cells and suppress the ... ...

Abstract	A family of transcription factors known as E proteins, and their antagonists, Id proteins, regulate T cell differentiation at critical developmental checkpoints. Id proteins promote the differentiation of conventional αβ T cells and suppress the expansion of innate-like αβ T cells known as invariant natural killer T (iNKT) cells. However, it remains to be determined whether Id proteins differentially regulate these distinct lineage choices in early stages of T cell development. In this manuscript, we report that in Id-deficient mice, uninhibited activity of the E protein family member E2A mediates activation of genes that support iNKT cell development and function. There is also biased rearrangement in Id-deficient DP cells that promotes selection into the iNKT lineage in these mice. The observed expansion of iNKT cells is not abrogated by blocking pre-TCR signaling, which is required for conventional αβ T cell development. Finally, E2A is found to be a key transcriptional regulator of both iNKT and γδNKT lineages, which appear to have shared lineage history. Therefore, our study reveals a previously unappreciated role of E2A in coordinating the development of the iNKT lineage at an early stage, prior to their TCR-mediated selection alongside conventional αβ T cells.
MeSH term(s)	Animals ; Basic Helix-Loop-Helix Transcription Factors/physiology ; Cell Differentiation ; Inhibitor of Differentiation Proteins/physiology ; Mice, Knockout ; Natural Killer T-Cells/physiology ; Receptors, Antigen, T-Cell/physiology
Chemical Substances	Basic Helix-Loop-Helix Transcription Factors ; Inhibitor of Differentiation Proteins ; Receptors, Antigen, T-Cell ; Tcf3 protein, mouse
Language	English
Publishing date	2018-01-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2018.00042
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Article ; Online: Non-Hodgkin Lymphomas: Malignancies Arising from Mature B Cells.

Shingleton, Jennifer / Wang, Jie / Baloh, Carolyn / Dave, Tushar / Davis, Nicholas / Happ, Lanie / Jadi, Othmane / Kositsky, Rachel / Li, Xiang / Love, Cassandra / Panea, Razvan / Qin, Qiu / Reddy, Anupama / Singhi, Naina / Smith, Eileen / Thakkar, Devang / Dave, Sandeep S

Cold Spring Harbor perspectives in medicine

2021 Volume 11, Issue 3

Abstract: Non-Hodgkin lymphomas (NHLs) are a diverse group of entities, both clinically and molecularly. Here, we review the evolution of classification schemes in B-cell lymphoma, noting the now standard WHO classification system that is based on immune cell-of- ... ...

Abstract	Non-Hodgkin lymphomas (NHLs) are a diverse group of entities, both clinically and molecularly. Here, we review the evolution of classification schemes in B-cell lymphoma, noting the now standard WHO classification system that is based on immune cell-of-origin and molecular phenotypes. We review how lymphomas arise throughout the B-cell development process as well as the molecular and clinical features of prominent B-cell lymphomas. We provide an overview of the major progress that has occurred over the past decade in terms of our molecular understanding of these diseases. We discuss treatment options available and focus on a number of the diverse research tools that have been employed to improve our understanding of these diseases. We discuss the problem of heterogeneity in lymphomas and anticipate that the near future will bring significant advances that provide a measurable impact on NHL outcomes.
MeSH term(s)	B-Lymphocytes/pathology ; Humans ; Lymphoma, B-Cell/classification ; Lymphoma, B-Cell/therapy ; Lymphoma, Non-Hodgkin/classification ; Lymphoma, Non-Hodgkin/therapy ; World Health Organization
Language	English
Publishing date	2021-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ISSN	2157-1422
ISSN (online)	2157-1422
DOI	10.1101/cshperspect.a034843
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Article ; Online: PD-L1 expression is low in large B-cell lymphoma with MYC or double-hit translocation.

Elbaek, Mette Vestergaard / Pedersen, Mette Ølgod / Breinholt, Marie Fredslund / Reddy, Anupama / Love, Cassandra / Clasen-Linde, Erik / Knudsen, Helle / Nielsen, Signe Ledou / Gang, Anne Ortved / Høgdall, Estrid / Dave, Sandeep / Nørgaard, Peter

Hematological oncology

2019 Volume 37, Issue 4, Page(s) 375–382

Abstract: In large B-cell lymphoma (LBCL), MYC translocation and MYC/BCL2 or MYC/BCL6 double hit (DH) are associated with poor prognosis, and there is an unmet need for novel treatment targets in this patient group. Treatments targeting the PD-L1/PD-1 pathway are ... ...

Abstract	In large B-cell lymphoma (LBCL), MYC translocation and MYC/BCL2 or MYC/BCL6 double hit (DH) are associated with poor prognosis, and there is an unmet need for novel treatment targets in this patient group. Treatments targeting the PD-L1/PD-1 pathway are still poorly elucidated in LBCL. PD-L1 expression might predict response to treatment targeting the PD-L1/PD-1 pathway. We therefore investigated the relationship between PD-L1 protein and mRNA expression levels and MYC and DH translocation in LBCL. We detected MYC, BCL2, and BCL6 translocation by fluorescent in situ hybridization in tissue samples from 130 patients randomly selected from two cohorts of patients with LBCL: 49 patients with MYC translocation of whom 36 had DH and 81 without MYC translocation. PD-L1 protein expression was detected by immunohistochemistry (IHC) in tissue samples from 77 patients and PD-L1 mRNA expression by next-generation RNA sequencing (NGS) in another 77 patients. Twenty-four patients overlapped, ie, were analysed with both IHC and NGS. Nonparametric tests were performed to evaluate intergroup differences. PD-L1 protein expression level was significantly lower in patients with MYC (n = 42, median = 3.3%, interquartile range [IQR] 0.0-10.8) or DH translocations (n = 31, median = 3.3%, IQR 0.0-10.0) compared with patients with no MYC (n = 35, median = 16.7%, IQR 3.3-30.0) or no DH translocations (n = 46, 13.3%, IQR 2.5-30.0), P = .004 and P ≤ .001, respectively. PD-L1 mRNA expression was also significantly lower in patients with MYC or DH translocations, P = .001 and P = .006, respectively. Higher PD-L1 protein and mRNA expression levels were associated with non-germinal centre (GC) type compared with germinal centre B-cell (GCB)-type diffuse LBCL (DLBCL), P = .004 and P = .002, respectively. In conclusion, we report an association between low PD-L1 expression and MYC and DH translocation in patients with LBCL. Our findings may indicate that patients with MYC or DH translocation may benefit less from treatment with PD-L1/PD-1-inhibitors compared with patients without these translocations. This should be evaluated in larger, prospective, consecutive trials.
MeSH term(s)	Adult ; Aged ; B-Lymphocyte Subsets/metabolism ; B-Lymphocyte Subsets/pathology ; B7-H1 Antigen/biosynthesis ; B7-H1 Antigen/genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, bcl-2 ; Genes, myc ; Germinal Center/pathology ; High-Throughput Nucleotide Sequencing ; Humans ; Lymphoma, Large B-Cell, Diffuse/metabolism ; Lymphoma, Large B-Cell, Diffuse/mortality ; Lymphoma, Large B-Cell, Diffuse/pathology ; Male ; Middle Aged ; Neoplasm Proteins/biosynthesis ; Neoplasm Proteins/genetics ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Proto-Oncogene Proteins c-bcl-6/genetics ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; RNA, Neoplasm/biosynthesis ; RNA, Neoplasm/genetics ; Retrospective Studies ; Translocation, Genetic
Chemical Substances	B7-H1 Antigen ; BCL6 protein, human ; CD274 protein, human ; Neoplasm Proteins ; Proto-Oncogene Proteins c-bcl-6 ; RNA, Messenger ; RNA, Neoplasm
Language	English
Publishing date	2019-08-25
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	604884-5
ISSN	1099-1069 ; 0278-0232
ISSN (online)	1099-1069
ISSN	0278-0232
DOI	10.1002/hon.2664
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Article ; Online: Injury promotes sarcoma development in a genetically and temporally restricted manner.

Van Mater, David / Xu, Eric / Reddy, Anupama / Añó, Leonor / Sachdeva, Mohit / Huang, Wesley / Williams, Nerissa / Ma, Yan / Love, Cassandra / Happ, Lanie / Dave, Sandeep / Kirsch, David G

JCI insight

2018 Volume 3, Issue 20

Abstract: Cancer results from the accumulation of genetic mutations in a susceptible cell of origin. We and others have also shown that injury promotes sarcoma development, but how injury cooperates with genetic mutations at the earliest stages of tumor formation ... ...

Abstract	Cancer results from the accumulation of genetic mutations in a susceptible cell of origin. We and others have also shown that injury promotes sarcoma development, but how injury cooperates with genetic mutations at the earliest stages of tumor formation is not known. Here, we utilized dual recombinase technology to dissect the complex interplay of the timing of KrasG12D activation, p53 deletion, and muscle injury in sarcomagenesis using a primary mouse model of soft tissue sarcoma. When mutations in oncogenic Kras and p53 are separated by 3 weeks, few sarcomas develop without injury. However, the transformation potential of these tumor-initiating cells can be unmasked by muscle injury. In the absence of Kras mutations, injury of the muscle with global deletion of p53 results in sarcomas with amplification of chromosomal regions encompassing the Met or Yap1 gene. These findings demonstrate a complex interplay between the timing of genetic mutations and perturbations in the tumor microenvironment, which provides insight into the earliest stages of sarcoma development.
MeSH term(s)	Animals ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; DNA Nucleotidyltransferases/genetics ; Disease Models, Animal ; Integrases/genetics ; Mice ; Mice, Transgenic ; Muscle Neoplasms/etiology ; Muscle, Skeletal/injuries ; Mutation ; Proto-Oncogene Proteins p21(ras)/genetics ; Sarcoma, Experimental/etiology ; Time Factors ; Tumor Microenvironment/genetics ; Tumor Suppressor Protein p53/genetics ; Wounds and Injuries/complications
Chemical Substances	Trp53 protein, mouse ; Tumor Suppressor Protein p53 ; Cre recombinase (EC 2.7.7.-) ; DNA Nucleotidyltransferases (EC 2.7.7.-) ; FLP recombinase (EC 2.7.7.-) ; Integrases (EC 2.7.7.-) ; Hras protein, mouse (EC 3.6.5.2) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
Language	English
Publishing date	2018-10-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.123687
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Article ; Online: Molecular characterization of circulating plasma cells in patients with active systemic lupus erythematosus.

Lugar, Patricia L / Love, Cassandra / Grammer, Amrie C / Dave, Sandeep S / Lipsky, Peter E

PloS one

2012 Volume 7, Issue 9, Page(s) e44362

Abstract: Systemic lupus erythematosus (SLE) is a generalized autoimmune disease characterized by abnormal B cell activation and the occurrence of increased frequencies of circulating plasma cells (PC). The molecular characteristics and nature of circulating PC ... ...

Abstract	Systemic lupus erythematosus (SLE) is a generalized autoimmune disease characterized by abnormal B cell activation and the occurrence of increased frequencies of circulating plasma cells (PC). The molecular characteristics and nature of circulating PC and B cells in SLE have not been completely characterized. Microarray analysis of gene expression was used to characterize circulating PC in subjects with active SLE. Flow cytometry was used to sort PC and comparator B cell populations from active SLE blood, normal blood and normal tonsil. The gene expression profiles of the sorted B cell populations were then compared. SLE PC exhibited a similar gene expression signature as tonsil PC. The differences in gene expression between SLE PC and normal tonsil PC and tonsil plasmablasts (PB) suggest a mature Ig secreting cell phenotype in the former population. Despite this, SLE PC differed in expression of about half the genes from previously published gene expression profiles of normal bone marrow PC, indicating that these cells had not achieved a fully mature status. Abnormal expression of several genes, including CXCR4 and S1P(1), suggests a mechanism for the persistence of SLE PC in the circulation. All SLE B cell populations revealed an interferon (IFN) gene signature previously only reported in unseparated SLE peripheral blood mononuclear cells. These data indicate that SLE PC are a unique population of Ig secreting cells with a gene expression profile indicative of a mature, but not fully differentiated phenotype.
MeSH term(s)	Cells, Cultured ; Child ; Child, Preschool ; Female ; Flow Cytometry ; Humans ; Immunoglobulins/metabolism ; Leukocytes, Mononuclear/metabolism ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/metabolism ; Male ; Palatine Tonsil/cytology ; Plasma Cells/metabolism ; Receptors, CXCR4/metabolism ; Receptors, Lysosphingolipid/metabolism
Chemical Substances	CXCR4 protein, human ; Immunoglobulins ; Receptors, CXCR4 ; Receptors, Lysosphingolipid
Language	English
Publishing date	2012-09-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0044362
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Article ; Online: Id2 Collaborates with Id3 To Suppress Invariant NKT and Innate-like Tumors.

Li, Jia / Roy, Sumedha / Kim, Young-Mi / Li, Shibo / Zhang, Baojun / Love, Cassandra / Reddy, Anupama / Rajagopalan, Deepthi / Dave, Sandeep / Diehl, Anna Mae / Zhuang, Yuan

Journal of immunology (Baltimore, Md. : 1950)

2017 Volume 198, Issue 8, Page(s) 3136–3148

Abstract: Inhibitor of DNA binding (Id) proteins, including Id1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins is associated with a broad spectrum of tumors, ... ...

Abstract	Inhibitor of DNA binding (Id) proteins, including Id1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins is associated with a broad spectrum of tumors, recent studies have identified that Id3 plays a tumor-suppressor role in the development of Burkitt's lymphoma in humans and hepatosplenic T cell lymphomas in mice. In this article, we report rapid lymphoma development in
MeSH term(s)	Adoptive Transfer ; Animals ; Cell Separation ; Cell Transformation, Neoplastic/immunology ; Cell Transformation, Neoplastic/metabolism ; Disease Models, Animal ; Flow Cytometry ; Humans ; Inhibitor of Differentiation Protein 2/immunology ; Inhibitor of Differentiation Proteins/immunology ; Lymphoma/immunology ; Lymphoma/pathology ; Mice ; Mice, Knockout ; Natural Killer T-Cells/immunology ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; T-Lymphocyte Subsets/immunology
Chemical Substances	Idb2 protein, mouse ; Inhibitor of Differentiation Protein 2 ; Inhibitor of Differentiation Proteins ; Idb3 protein, mouse (135845-89-5)
Language	English
Publishing date	2017-04-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1601935
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Article ; Online: Human Mesenchymal Stem Cell-Educated Macrophages Are a Distinct High IL-6-Producing Subset that Confer Protection in Graft-versus-Host-Disease and Radiation Injury Models.

Bouchlaka, Myriam N / Moffitt, Andrea B / Kim, Jaehyup / Kink, John A / Bloom, Debra D / Love, Cassandra / Dave, Sandeep / Hematti, Peiman / Capitini, Christian M

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

2017 Volume 23, Issue 6, Page(s) 897–905

Abstract: Mesenchymal stem cells (MSCs) have immunosuppressive and tissue repair properties, but clinical trials using MSCs to prevent or treat graft-versus-host disease (GVHD) have shown mixed results. Macrophages (MØs) are important regulators of immunity and ... ...

Abstract	Mesenchymal stem cells (MSCs) have immunosuppressive and tissue repair properties, but clinical trials using MSCs to prevent or treat graft-versus-host disease (GVHD) have shown mixed results. Macrophages (MØs) are important regulators of immunity and can promote tissue regeneration and remodeling. We have previously shown that MSCs can educate MØs toward a unique anti-inflammatory immunophenotype (MSC-educated MØs [MEMs]); however, their implications for in vivo models of inflammation have not been studied yet. We now show that in comparison with MØs, MEMs have increased expression of the inhibitory molecules PD-L1, PD-L2, in addition to markers of alternatively activated MØs: CD206 and CD163. RNA-Seq analysis of MEMs, as compared with MØs, show a distinct gene expression profile that positively correlates with multiple pathways important in tissue repair. MEMs also show increased expression of IL-6, transforming growth factor-β, arginase-1, CD73, and decreased expression of IL-12 and tumor necrosis factor-α. We show that IL-6 secretion is controlled in part by the cyclo-oxygenase-2, arginase, and JAK1/STAT1 pathway. When tested in vivo, we show that human MEMs significantly enhance survival from lethal GVHD and improve survival of mice from radiation injury. We show these effects could be mediated in part through suppression of human T cell proliferation and may have attenuated host tissue injury in part by enhancing murine fibroblast proliferation. MEMs are a unique MØ subset with therapeutic potential for the management of GVHD and/or protection from radiation-induced injury.
MeSH term(s)	Animals ; Cell Communication/immunology ; Cell- and Tissue-Based Therapy/methods ; Graft vs Host Disease/therapy ; Humans ; Inflammation/immunology ; Interleukin-6/biosynthesis ; Macrophage Activation/immunology ; Macrophages/cytology ; Macrophages/immunology ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/immunology ; Mice ; Radiation Injuries/therapy
Chemical Substances	Interleukin-6
Language	English
Publishing date	2017-02-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1474865-4
ISSN	1523-6536 ; 1083-8791
ISSN (online)	1523-6536
ISSN	1083-8791
DOI	10.1016/j.bbmt.2017.02.018
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Zs.A 5082: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: PAK1 mediates resistance to PI3K inhibition in lymphomas.

Walsh, Katherine / McKinney, Matthew S / Love, Cassandra / Liu, Qingquan / Fan, Alice / Patel, Amee / Smith, Jason / Beaven, Anne / Jima, Dereje D / Dave, Sandeep S

Clinical cancer research : an official journal of the American Association for Cancer Research

2013 Volume 19, Issue 5, Page(s) 1106–1115

Abstract: Purpose: The phosphoinositide 3-kinase (PI3K) pathway is known to play an active role in many malignancies. The role of PI3K inhibition in the treatment of lymphomas has not been fully delineated. We sought to identify a role for therapeutic PI3K ... ...

Abstract	Purpose: The phosphoinositide 3-kinase (PI3K) pathway is known to play an active role in many malignancies. The role of PI3K inhibition in the treatment of lymphomas has not been fully delineated. We sought to identify a role for therapeutic PI3K inhibition across a range of B-cell lymphomas. Experimental design: We selected three small molecule inhibitors to test in a panel of 60 cell lines that comprised diverse lymphoma types. We tested the selective PI3K inhibitor BKM120 and the dual PI3K/mTOR inhibitors BEZ235 and BGT226 in these cell lines. We applied gene expression profiling to better understand the molecular mechanisms associated with responsiveness to these drugs. Results: We found that higher expression of the PAK1 gene was significantly associated with resistance to all three PI3K inhibitors. Through RNA-interference-mediated knockdown of the PAK1 gene, we showed a dramatic increase in the sensitivity to PI3K inhibition. We further tested a small-molecule inhibitor of PAK1 and found significant synergy between PI3K and PAK1 inhibition. Conclusion: Thus, we show that PI3K inhibition is broadly effective in lymphomas and PAK1 is a key modulator of resistance to PI3K inhibition.
MeSH term(s)	Aminopyridines/pharmacology ; Biomarkers, Tumor/genetics ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm/drug effects ; Drug Synergism ; Enzyme Inhibitors/pharmacology ; Gene Expression Profiling ; Humans ; Imidazoles/pharmacology ; Lymphoma/drug therapy ; Lymphoma/genetics ; Lymphoma/metabolism ; Morpholines/pharmacology ; Oligonucleotide Array Sequence Analysis ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Quinolines/pharmacology ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Small Molecule Libraries ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; TOR Serine-Threonine Kinases/metabolism ; Tumor Cells, Cultured ; p21-Activated Kinases/antagonists & inhibitors ; p21-Activated Kinases/genetics ; p21-Activated Kinases/metabolism
Chemical Substances	8-(6-methoxypyridin-3-yl)-3-methyl-1-(4-piperazin-1-yl-3-trifluoromethylphenyl)-1,3-dihydroimidazo(4,5-c)quinolin-2-one ; Aminopyridines ; Biomarkers, Tumor ; Enzyme Inhibitors ; Imidazoles ; Morpholines ; NVP-BKM120 ; Phosphoinositide-3 Kinase Inhibitors ; Quinolines ; RNA, Messenger ; RNA, Small Interfering ; Small Molecule Libraries ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; PAK1 protein, human (EC 2.7.11.1) ; p21-Activated Kinases (EC 2.7.11.1) ; dactolisib (RUJ6Z9Y0DT)
Language	English
Publishing date	2013-01-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-12-1060
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Article ; Online: The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells.

Zhang, Jenny / Jima, Dereje / Moffitt, Andrea B / Liu, Qingquan / Czader, Magdalena / Hsi, Eric D / Fedoriw, Yuri / Dunphy, Cherie H / Richards, Kristy L / Gill, Javed I / Sun, Zhen / Love, Cassandra / Scotland, Paula / Lock, Eric / Levy, Shawn / Hsu, David S / Dunson, David / Dave, Sandeep S

Blood

2014 Volume 123, Issue 19, Page(s) 2988–2996

Abstract: In this study, we define the genetic landscape of mantle cell lymphoma (MCL) through exome sequencing of 56 cases of MCL. We identified recurrent mutations in ATM, CCND1, MLL2, and TP53. We further identified a number of novel genes recurrently mutated ... ...

Abstract	In this study, we define the genetic landscape of mantle cell lymphoma (MCL) through exome sequencing of 56 cases of MCL. We identified recurrent mutations in ATM, CCND1, MLL2, and TP53. We further identified a number of novel genes recurrently mutated in patients with MCL including RB1, WHSC1, POT1, and SMARCA4. We noted that MCLs have a distinct mutational profile compared with lymphomas from other B-cell stages. The ENCODE project has defined the chromatin structure of many cell types. However, a similar characterization of primary human mature B cells has been lacking. We defined, for the first time, the chromatin structure of primary human naïve, germinal center, and memory B cells through chromatin immunoprecipitation and sequencing for H3K4me1, H3K4me3, H3Ac, H3K36me3, H3K27me3, and PolII. We found that somatic mutations that occur more frequently in either MCLs or Burkitt lymphomas were associated with open chromatin in their respective B cells of origin, naïve B cells, and germinal center B cells. Our work thus elucidates the landscape of gene-coding mutations in MCL and the critical interplay between epigenetic alterations associated with B-cell differentiation and the acquisition of somatic mutations in cancer.
MeSH term(s)	Ataxia Telangiectasia Mutated Proteins/genetics ; B-Lymphocytes/metabolism ; Burkitt Lymphoma/genetics ; Burkitt Lymphoma/pathology ; Chromatin/genetics ; Chromatin/metabolism ; Cyclin D1/genetics ; DNA Helicases/genetics ; DNA-Binding Proteins/genetics ; Epigenesis, Genetic ; Exome/genetics ; Gene Regulatory Networks ; Genomics ; Germinal Center/metabolism ; Germinal Center/pathology ; Histone-Lysine N-Methyltransferase/genetics ; Histones/genetics ; Histones/metabolism ; Humans ; Lymphoma, Mantle-Cell/genetics ; Lymphoma, Mantle-Cell/pathology ; Methylation ; Mutation ; Neoplasm Proteins/genetics ; Nuclear Proteins/genetics ; Repressor Proteins/genetics ; Retinoblastoma Protein/genetics ; Sequence Analysis, DNA ; Telomere-Binding Proteins/genetics ; Transcription Factors/genetics ; Tumor Suppressor Protein p53/genetics
Chemical Substances	Chromatin ; DNA-Binding Proteins ; Histones ; KMT2D protein, human ; Neoplasm Proteins ; Nuclear Proteins ; POT1 protein, human ; Repressor Proteins ; Retinoblastoma Protein ; Telomere-Binding Proteins ; Transcription Factors ; Tumor Suppressor Protein p53 ; Cyclin D1 (136601-57-5) ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43) ; NSD2 protein, human (EC 2.1.1.43) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; SMARCA4 protein, human (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-)
Language	English
Publishing date	2014-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2013-07-517177
Database	MEDical Literature Analysis and Retrieval System OnLINE

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