"Alternative Splicing Microarrays Reveal Functional Expression of Neuron-specific Regulators in Hodgkin Lymphoma Cells"*

Angela Relógio ^{1, 2}, Claudia Ben-Dov ¶, Michael Baum ||, Matteo Ruggiu**, Christine Gemund ¹, Vladimir Benes ¹ , Robert B. Darnell**, and Juan Valcárcel ¶ ^@

¹ European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany, 
¶Centre de Regulació Genòmica, Passeig Marítim 37-49, 08003 Barcelona, Spain, 
||Febit, AG, 68167 Mannheim, Germany, and
**Rockefeller University, New York, New York 10021

^@ To whom correspondence should be addressed. Tel.: 34-93-224-09-56; Fax: 34-93-224-08-99;
E-mail:    juan.valcarcel@crg.es

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. 

* This work was supported in part by grants from Bundesministerium für Bildung und Forschung, European Union FP5, and Human Frontier Science Program Organization. The costs of publication of this article were
defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article ( available at: http://www.jbc.org/cgi/content/abstract/280/6/4779  ) contains a supplemental table.

² Recipient of a PRAXIS XXI fellowship from the Portuguese Foundation for Science and Technology.

^@To whom correspondence should be addressed. Tel.: 34-93-224-09-56; Fax: 34-93-224-08-99;
E-mail:   juan.valcarcel@crg.es

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