title: Prognostically relevant gene signatures of high-grade serous ovarian carcinoma.
abstract: Because of the high risk of recurrence in high-grade serous ovarian carcinoma (HGS-OvCa), the development of outcome predictors could be valuable for patient stratification. Using the catalog of The Cancer Genome Atlas (TCGA), we developed subtype and survival gene expression signatures, which, when combined, provide a prognostic model of HGS-OvCa classification, named "Classification of Ovarian Cancer" (CLOVAR). We validated CLOVAR on an independent dataset consisting of 879 HGS-OvCa expression profiles. The worst outcome group, accounting for 23% of all cases, was associated with a median survival of 23 months and a platinum resistance rate of 63%, versus a median survival of 46 months and platinum resistance rate of 23% in other cases. Associating the outcome prediction model with BRCA1/BRCA2 mutation status, residual disease after surgery, and disease stage further optimized outcome classification. Ovarian cancer is a disease in urgent need of more effective therapies. The spectrum of outcomes observed here and their association with CLOVAR signatures suggests variations in underlying tumor biology. Prospective validation of the CLOVAR model in the context of additional prognostic variables may provide a rationale for optimal combination of patient and treatment regimens.
authors.affiliation: Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, Texas 77030, USA. rverhaak@mdanderson.org
authors.forename: Roel G W
authors.initials: RG
authors.lastname: Verhaak
authors.forename: Pablo
authors.initials: P
authors.lastname: Tamayo
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Yang
authors.forename: Diana
authors.initials: D
authors.lastname: Hubbard
authors.forename: Hailei
authors.initials: H
authors.lastname: Zhang
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.forename: Sian
authors.initials: S
authors.lastname: Fereday
authors.forename: Michael
authors.initials: M
authors.lastname: Lawrence
authors.forename: Scott L
authors.initials: SL
authors.lastname: Carter
authors.forename: Craig H
authors.initials: CH
authors.lastname: Mermel
authors.forename: Aleksandar D
authors.initials: AD
authors.lastname: Kostic
authors.forename: Dariush
authors.initials: D
authors.lastname: Etemadmoghadam
authors.forename: Gordon
authors.initials: G
authors.lastname: Saksena
authors.forename: Kristian
authors.initials: K
authors.lastname: Cibulskis
authors.forename: Sekhar
authors.initials: S
authors.lastname: Duraisamy
authors.forename: Keren
authors.initials: K
authors.lastname: Levanon
authors.forename: Carrie
authors.initials: C
authors.lastname: Sougnez
authors.forename: Aviad
authors.initials: A
authors.lastname: Tsherniak
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gomez
authors.forename: Robert
authors.initials: R
authors.lastname: Onofrio
authors.forename: Stacey
authors.initials: S
authors.lastname: Gabriel
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.forename: Nianxiang
authors.initials: N
authors.lastname: Zhang
authors.forename: Paul T
authors.initials: PT
authors.lastname: Spellman
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rehan
authors.initials: R
authors.lastname: Akbani
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hoadley
authors.forename: Ari
authors.initials: A
authors.lastname: Kahn
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
authors.forename: David
authors.initials: D
authors.lastname: Huntsman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Soslow
authors.forename: Anna
authors.initials: A
authors.lastname: Defazio
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Birrer
authors.forename: Joe W
authors.initials: JW
authors.lastname: Gray
authors.forename: John N
authors.initials: JN
authors.lastname: Weinstein
authors.forename: David D
authors.initials: DD
authors.lastname: Bowtell
authors.forename: Ronny
authors.initials: R
authors.lastname: Drapkin
authors.forename: Jill P
authors.initials: JP
authors.lastname: Mesirov
authors.forename: Gad
authors.initials: G
authors.lastname: Getz
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Levine
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000096:biosynthesis / Q000235:genetics; D024682:BRCA2 Protein / Q000096:biosynthesis / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D009154:Mutation; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human