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Multiple Alternative Splicing Markers for Ovarian Cancer

¹ Laboratoire de génomique fonctionnelle de l'Université de Sherbrooke, ² Département de pathologie, and ³ Département de microbiologie et d'infectiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, Canada

Requests for reprints: Sherif Abou Elela, Département de microbiologie et d'infectiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, Québec, Canada J1H 5N4. Phone: 819-564-5275; E-mail: sherif.abou.elela{at}usherbrooke.ca.

Key Words: alternative splicing • ovarian cancer • RT-PCR • genomics • Rnomics

Intense efforts are currently being directed toward profiling gene expression in the hope of developing better cancer markers and identifying potential drug targets. Here, we present a sensitive new approach for the identification of cancer signatures based on direct high-throughput reverse transcription-PCR validation of alternative splicing events. This layered and integrated system for splicing annotation (LISA) fills a gap between high-throughput microarray studies and high-sensitivity individual gene investigations, and was created to monitor the splicing of 600 cancer-associated genes in 25 normal and 21 serous ovarian cancer tissues. Out of >4,700 alternative splicing events screened, the LISA identified 48 events that were significantly associated with serous ovarian tumor tissues. In a further screen directed at 39 ovarian tissues containing cancer pathologies of various origins, our ovarian cancer splicing signature successfully distinguished all normal tissues from cancer. High-volume identification of cancer-associated splice forms by the LISA paves the way for the use of alternative splicing profiling to diagnose subtypes of cancer. [Cancer Res 2008;68(3):657–63]

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