Multiple alternative splicing markers for ovarian cancer.
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.
Klinck
Roscoe
R
Laboratoire de génomique fonctionnelle de l'Université de Sherbrooke, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Bramard
Anne
A
Inkel
Lyna
L
Dufresne-Martin
Geneviève
G
Gervais-Bird
Julien
J
Madden
Richard
R
Paquet
Eric R
ER
Koh
ChuShin
C
Venables
Julian P
JP
Prinos
Panagiotis
P
Jilaveanu-Pelmus
Manuela
M
Wellinger
Raymund
R
Rancourt
Claudine
C
Chabot
Benoit
B
Abou Elela
Sherif
S
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*
D012333:RNA, Messenger