Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE).
Clin Cancer Res 2020 Oct 15; 26(20):5411-5423
PURPOSE: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features.
EXPERIMENTAL DESIGN: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting.
RESULTS: Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a
CONCLUSIONS: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications.
Talhouk, Aline; George, Joshy; Wang, Chen; Budden, Timothy; Tan, Tuan Zea; Chiu, Derek S; Kommoss, Stefan; Leong, Huei San; Chen, Stephanie; Intermaggio, Maria P; Gilks, Blake; Nazeran, Tayyebeh M; Volchek, Mila; Elatre, Wafaa; Bentley, Rex C; Senz, Janine; Lum, Amy; Chow, Veronica; Sudderuddin, Hanwei; Mackenzie, Robertson; Leong, Samuel C Y; Liu, Geyi; Johnson, Dustin; Chen, Billy; Group, Aocs; Alsop, Jennifer; Banerjee, Susana N; Behrens, Sabine; Bodelon, Clara; Brand, Alison H; Brinton, Louise; Carney, Michael E; Chiew, Yoke-Eng; Cushing-Haugen, Kara L; Cybulski, Cezary; Ennis, Darren; Fereday, Sian; Fortner, Renée T; García-Donas, Jesús; Gentry-Maharaj, Aleksandra; Glasspool, Rosalind; Goranova, Teodora; Greene, Casey S; Haluska, Paul; Harris, Holly R; Hendley, Joy; Hernandez, Brenda Y; Herpel, Esther; Jimenez-Linan, Mercedes; Karpinskyj, Chloe; Kaufmann, Scott H; Keeney, Gary L; Kennedy, Catherine J; Köbel, Martin; Koziak, Jennifer M; Larson, Melissa C; Lester, Jenny; Lewsley, Liz-Anne; Lissowska, Jolanta; Lubiński, Jan; Luk, Hugh; Macintyre, Geoff; Mahner, Sven; McNeish, Iain A; Menkiszak, Janusz; Nevins, Nikilyn; Osorio, Ana; Oszurek, Oleg; Palacios, José; Hinsley, Samantha; Pearce, Celeste L; Pike, Malcolm C; Piskorz, Anna M; Ray-Coquard, Isabelle; Rhenius, Valerie; Rodriguez-Antona, Cristina; Sharma, Raghwa; Sherman, Mark E; De Silva, Dilrini; Singh, Naveena; Sinn, Peter; Slamon, Dennis; Song, Honglin; Steed, Helen; Stronach, Euan A; Thompson, Pamela J; Tołoczko, Aleksandra; Trabert, Britton; Traficante, Nadia; Tseng, Chiu-Chen; Widschwendter, Martin; Wilkens, Lynne R; Winham, Stacey J; Winterhoff, Boris; Beeghly-Fadiel, Alicia; Benitez, Javier; Berchuck, Andrew; Brenton, James D; Brown, Robert; Chang-Claude, Jenny; Chenevix-Trench, Georgia; deFazio, Anna; Fasching, Peter A; García, María J; Gayther, Simon A; Goodman, Marc T; Gronwald, Jacek; Henderson, Michelle J; Karlan, Beth Y; Kelemen, Linda E; Menon, Usha; Orsulic, Sandra; Pharoah, Paul D P; Wentzensen, Nicolas; Wu, Anna H; Schildkraut, Joellen M; Rossing, Mary Anne; Konecny, Gottfried E; Huntsman, David G; Huang, Ruby Yun-Ju; Goode, Ellen L; Ramus, Susan J; Doherty, Jennifer A; Bowtell, David D; and Anglesio, Michael S, "Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE)." (2020). Faculty Research 2020. 194.