scholarly journals Gene Expression Profiling of Lung Atypical Carcinoids and Large Cell Neuroendocrine Carcinomas Identifies Three Transcriptomic Subtypes with Specific Genomic Alterations

2019 ◽  
Vol 14 (9) ◽  
pp. 1651-1661 ◽  
Author(s):  
Michele Simbolo ◽  
Stefano Barbi ◽  
Matteo Fassan ◽  
Andrea Mafficini ◽  
Greta Ali ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Large Cell ◽  
Genomic Alterations ◽  
Neuroendocrine Carcinomas

Gene Expression Profiling Reveals a Crucial Role for C/EBPbeta in Proliferation Pathways of ALK+ ALCL Cell Lines

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2818-2818
Author(s):  
Irina Bonzheim ◽  
Martin Irmler ◽  
Natasa Anastasov ◽  
Margit Klier ◽  
Johannes Beckers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Statistical Analysis ◽  
Gene Expression Profiling ◽  
Cell Lines ◽  
Expression Profiling ◽  
Leucine Zipper ◽  
Cellular Proliferation ◽  
Kinase Activity ◽  
Large Cell

Abstract Introduction: ALK+ anaplastic large cell lymphomas (ALCL) overexpress C/EBPβ, as a consequence of NPM-ALK kinase activity. C/EBPβ is a leucine zipper transcription factor, which plays a major role in cellular differentiation, inflammation, proliferation and metabolism control. To determine the role of C/EBPβ in ALK+ ALCL transformation, and to identify its downstream targets, a highly specific C/EBPβ-shRNA was used to knockdown C/EBPβ. The consequences of C/EBPβ gene-silencing were analyzed by gene expression profiling. Materials and Methods: Four ALK+ ALCL cell lines, SUDHL-1, Kijk, Karpas 299 and SUP-M2 were transfected with lentivirus containing the C/EBPβ shRNA or the vector without shRNA in triplicates. Western Blot analysis and qRT-PCR were performed to quantify the knockdown effect. At day three after infection, RNA was extracted and used for Gene Chip expression analysis (Affymetrix). Using Anova software for statistical analysis, we identified genes, which were regulated in all four cell lines. The effect of C/EBPβ knockdown on proliferation, cell cycle, and viability was analyzed by MTT assay and FACS analysis. Results: In all four ALK+ ALCL, efficient C/EBPβ knockdown resulted in profound growth retardation (up to 84%) compared to control cells after 6 days of infection, and a clear shift from the S phase to the G1 phase in the cell cycle was observed. To identify genes regulated by C/EBPβ in all four cell lines, we performed statistical analysis applying a false discovery rate of 20%, and accepted only genes with a >1,1 and <0,9 fold ratio. We identfied 435 genes regulated after C/EBPβ knockdown (117 upregulated, 318 downregulated). Classification of the differentially expressed genes into biological categories revealed overrepresentation of genes involved in the regulation of kinase activity, cell cycle and proliferation, lymphocyte differentiation, and metabolic processes. In particular, kinases involved in the regulation of JNK activity, which have been shown previously to be involved in proliferation of ALCL, were highly affected by C/EBPβ knockdown. Genomatix Bibliosphere Pathway Analysis revealed C/EBPβ to be connected to pathways involving cell cycle (RUNX3, CCNG1, CDKN2A), apoptosis (FAS, PTPRC, BCL2A1, BIRC3) and MAPK cascades (TRIB1 and several MAP3Ks). Several of the genes identified contain known C/EBPβ binding sites. Conclusions: C/EBPβ silencing induces growth arrest in ALK+ALCL, which correlates with differential expression of genes involved in cell cycle, apoptosis and differentiation. This study reveals C/EBPβ as a master transcription regulator of NPM-ALK induced cellular proliferation, and therefore, an ideal candidate for targeted therapeutic intervention.

Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK+ subtypes

Blood ◽  
2006 ◽  
Vol 109 (5) ◽  
pp. 2156-2164 ◽  
Author(s):  
Laurence Lamant ◽  
Aurélien de Reyniès ◽  
Marie-Michèle Duplantier ◽  
David S. Rickman ◽  
Frédérique Sabourdy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Anaplastic Large Cell Lymphoma ◽  
Expression Profiling ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
Large Cell ◽  
Molecular Signature ◽  
Number Of Patients ◽  
Large Cell Lymphoma

Abstract With the use of microarray gene-expression profiling, we analyzed a homogeneous series of 32 patients with systemic anaplastic large-cell lymphoma (ALCL) and 5 ALCL cell lines. Unsupervised analysis classified ALCL in 2 clusters, corresponding essentially to morphologic subgroups (ie, common type vs small cell and “mixed” variants) and clinical variables. Patients with a morphologic variant of ALCL had advanced-stage disease. This group included a significant number of patients who experienced early relapse. Supervised analysis showed that ALK+ALCL and ALK− ALCL have different gene-expression profiles, further confirming that they are different entities. Among the most significantly differentially expressed genes between ALK+ and ALK− samples, we found BCL6, PTPN12, CEBPB, and SERPINA1 genes to be overexpressed in ALK+ ALCL. This result was confirmed at the protein level for BCL-6, C/EBPβ and serpinA1 through tissue microarrays. The molecular signature of ALK− ALCL included overexpression of CCR7, CNTFR, IL22, and IL21 genes but did not provide any obvious clues to the molecular mechanism underlying this tumor subtype. Once confirmed on a larger number of patients, the results of the present study could be used for clinical and therapeutic management of patients at the time of diagnosis.

Gene Expression Profiling in Anaplastic Large Cell Lymphoma and Hodgkin's Disease

2004 ◽  
Vol 45 (10) ◽  
pp. 2001-2006 ◽  
Author(s):  
Pascal Trempat ◽  
Claire Villalva ◽  
Luc Xerri ◽  
Florence Armstrong ◽  
Marie-Michele Duplantier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Anaplastic Large Cell Lymphoma ◽  
Hodgkin's Disease ◽  
Expression Profiling ◽  
Cell Lymphoma ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Large Cell Lymphoma

scholarly journals Gene Expression Profiling of Large Cell Lung Cancer Links Transcriptional Phenotypes to the New Histological WHO 2015 Classification

2017 ◽  
Vol 12 (8) ◽  
pp. 1257-1267 ◽  
Author(s):  
Anna Karlsson ◽  
Hans Brunnström ◽  
Patrick Micke ◽  
Srinivas Veerla ◽  
Johanna Mattsson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Gene Expression Profiling ◽  
Cell Lung Cancer ◽  
Expression Profiling ◽  
Large Cell ◽  
Large Cell Lung Cancer

scholarly journals Comparative gene-expression profiling of the large cell variant of gastrointestinal marginal-zone B-cell lymphoma

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Thomas F. E. Barth ◽  
Johann M. Kraus ◽  
Ludwig Lausser ◽  
Lucia Flossbach ◽  
Lukas Schulte ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Cell Variant

Gene Expression Profiling Uncovers Molecular Classifiers for the Recognition of Anaplastic Large-Cell Lymphoma Within Peripheral T-Cell Neoplasms

2010 ◽  
Vol 28 (9) ◽  
pp. 1583-1590 ◽  
Author(s):  
Roberto Piva ◽  
Luca Agnelli ◽  
Elisa Pellegrino ◽  
Katia Todoerti ◽  
Valentina Grosso ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Gene Expression Profiling ◽  
Cell Lines ◽  
Anaplastic Large Cell Lymphoma ◽  
Expression Profiling ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Large Cell Lymphoma ◽  
Alk Positive

Purpose To unravel the regulatory network underlying nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) –mediated lymphomagenesis of anaplastic large-cell lymphoma (ALCL) and to discover diagnostic genomic classifiers for the recognition of patients with ALK-positive and ALK-negative ALCL among T-cell non-Hodgkin's lymphoma (T-NHL). Patients and Methods The transcriptome of NPM-ALK–positive ALCL cell lines was characterized by silencing the expression of ALK or STAT3, a major effector of ALK oncogenic activity. Gene expression profiling (GEP) was performed in a series of systemic primary T-NHL (n = 70), including a set of ALK-positive and ALK-negative ALCL (n = 36). Genomic classifiers for ALK-positive and ALK-negative ALCL were generated by prediction analyses and validated by quantitative reverse-transcriptase polymerase chain reaction and/or immunohistochemistry. Results In ALCL cell lines, two thirds of ALK-regulated genes were concordantly dependent on STAT3 expression. GEP of systemic primary T-NHL significantly clustered ALK-positive ALCL samples in a separate subgroup, underscoring the relevance of in vitro ALK/STAT3 signatures. A set of genomic classifiers for ALK-positive ALCL and for ALCL were identified by prediction analyses. These gene clusters were instrumental for the distinction of ALK-negative ALCL from peripheral T-cell lymphomas not otherwise specified (PTCLs-NOS) and angioimmunoblastic lymphomas. Conclusion We proved that experimentally controlled GEP in ALCL cell lines represents a powerful tool to identify meaningful signaling networks for the recognition of systemic primary T-NHL. The identification of a molecular signature specific for ALCL suggests that these T-NHLs may represent a unique entity discernible from other PTCLs, and that a restricted number of genes can be instrumental for clinical stratification and, possibly, therapy of T-NHL.

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