title: Alternative splicing microarrays reveal functional expression of neuron-specific regulators in Hodgkin lymphoma cells.
abstract: Alternative splicing provides a versatile mechanism of gene regulation, which is often subverted in disease. We have used customized oligonucleotide microarrays to interrogate simultaneously the levels of expression of splicing factors and the patterns of alternative splicing of genes involved in tumor progression. Analysis of RNAs isolated from cell lines derived from Hodgkin lymphoma tumors indicate that the relative abundance of alternatively spliced isoforms correlates with transformation and tumor grade. Changes in expression of regulators were also detected, and a subset sample was confirmed at the protein level. Ectopic expression of neuron-specific splicing regulatory proteins of the Nova family was observed in some cell lines and tumor samples, correlating with expression of a neuron-specific mRNA isoform of JNK2 kinase. This microarray design can help assess the role of alternative splicing in a variety of biological and medical problems and potentially serve as a diagnostic tool.
authors.affiliation: European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Relógio
authors.forename: Claudia
authors.initials: C
authors.lastname: Ben-Dov
authors.forename: Michael
authors.initials: M
authors.lastname: Baum
authors.forename: Matteo
authors.initials: M
authors.lastname: Ruggiu
authors.forename: Christine
authors.initials: C
authors.lastname: Gemund
authors.forename: Vladimir
authors.initials: V
authors.lastname: Benes
authors.forename: Robert B
authors.initials: RB
authors.lastname: Darnell
authors.forename: Juan
authors.initials: J
authors.lastname: Valcárcel
mesh_terms: D017398:Alternative Splicing; D015153:Blotting, Western; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D019992:Databases as Topic; D006689:Hodgkin Disease / Q000378:metabolism*; D006801:Humans; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025803:Tumor Suppressor Protein p14ARF / Q000737:chemistry
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D018076:DNA, Complementary; D020033:Protein Isoforms; D012333:RNA, Messenger; D025803:Tumor Suppressor Protein p14ARF; D012313:RNA; D048056:Mitogen-Activated Protein Kinase 9