title: Multiple alternative splicing markers for ovarian cancer.
abstract: 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.
authors.affiliation: Laboratoire de génomique fonctionnelle de l'Université de Sherbrooke, Université de Sherbrooke, Sherbrooke, Québec, Canada.
authors.forename: Roscoe
authors.initials: R
authors.lastname: Klinck
authors.forename: Anne
authors.initials: A
authors.lastname: Bramard
authors.forename: Lyna
authors.initials: L
authors.lastname: Inkel
authors.forename: Geneviève
authors.initials: G
authors.lastname: Dufresne-Martin
authors.forename: Julien
authors.initials: J
authors.lastname: Gervais-Bird
authors.forename: Richard
authors.initials: R
authors.lastname: Madden
authors.forename: Eric R
authors.initials: ER
authors.lastname: Paquet
authors.forename: ChuShin
authors.initials: C
authors.lastname: Koh
authors.forename: Julian P
authors.initials: JP
authors.lastname: Venables
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Prinos
authors.forename: Manuela
authors.initials: M
authors.lastname: Jilaveanu-Pelmus
authors.forename: Raymund
authors.initials: R
authors.lastname: Wellinger
authors.forename: Claudine
authors.initials: C
authors.lastname: Rancourt
authors.forename: Benoit
authors.initials: B
authors.lastname: Chabot
authors.forename: Sherif
authors.initials: S
authors.lastname: Abou Elela
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D019295:Computational Biology / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*
chemical_list: D012333:RNA, Messenger