Journal Article

DKFZ-2020-01159

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Development and validation of the gene-expression Predictor of high-grade-serous Ovarian carcinoma molecular subTYPE (PrOTYPE).

Talhouk, A. ; George, J. ; Wang, C. ; Budden, T. ; Tan, T. Z. ; Chiu, D. S. ; Kommoss, S. ; Leong, H. S. ; Chen, S. ; Intermaggio, M. P. ; Gilks, B. ; Nazeran, T. M. ; Volchek, M. ; Elatre, W. ; Bentley, R. C. ; Senz, J. ; Lum, A. ; Chow, V. ; Sudderuddin, H. ; Mackenzie, R. ; Leung, S. ; Liu, G. ; Johnson, D. ; Chen, B. ; Ovarian Cancer Study, A. ; Alsop, J. ; Banerjee, S. ; Behrens, S.DKFZ* ; Bodelon, C. ; Brand, A. H. ; Brinton, L. A. ; Carney, M. E. ; Chiew, Y.-E. ; Cushing-Haugen, K. L. ; Cybulski, C. ; Ennis, D. ; Fereday, S. ; Turzanski-Fortner, R.DKFZ* ; García-Donás, J. ; Gentry-Maharaj, A. ; Glasspool, R. ; Goranova, T. ; Greene, C. S. ; Haluska, P. ; Harris, H. R. ; Hendley, J. ; Hernandez, B. Y. ; Herpel, E. ; Jimenez-Linan, M. ; Karpinskyj, C. ; Kaufmann, S. H. ; Keeney, G. ; Kennedy, C. J. ; Köbel, M. ; Koziak, J. ; Larson, M. C. ; Lester, J. ; Lewsley, L.-A. ; Lissowska, J. ; Lubiński, J. ; Luk, H. ; Macintyre, G. ; Mahner, S. ; McNeish, I. A. ; Menkiszak, J. ; Nevins, N. ; Osorio, A. ; Oszurek, O. ; Palacios, J. ; Hinsley, S. ; Pearce, C. L. ; Pike, M. C. ; Piskorz, A. ; Ray-Coquard, I. ; Rhenius, V. ; Rodríguez-Antona, C. ; Sharma, R. ; Sherman, M. E. ; Silva, D. ; Singh, N. ; Sinn, H.-P. ; Slamon, D. J. ; Song, H. ; Steed, H. ; Stronach, E. A. ; Thompson, P. J. ; Tołoczko-Grabarek, A. ; Trabert, B. ; Traficante, N. ; Tseng, C.-C. ; Widschwendter, M. ; Wilkens, L. R. ; Winham, S. J. ; Winterhoff, B. J. ; Beeghly-Fadiel, A. ; Benitez, J. ; Berchuck, A. ; Brenton, J. D. ; Brown, R. ; Chang-Claude, J.DKFZ* ; Chenevix-Trench, G. ; DeFazio, A. ; Fasching, P. A. ; Garcia, M. J. ; Gayther, S. A. ; Goodman, M. T. ; Gronwald, J. ; Henderson, M. J. ; Karlan, B. Y. ; Kelemen, L. E. ; Menon, U. ; Orsulic, S. ; Pharoah, P. D. P. ; Wentzensen, N. ; Wu, A. H. ; Shildkraut, J. ; Rossing, M. A. ; Konecny, G. E. ; Huntsman, D. G. ; Huang, R. Y. ; Goode, E. L. ; Ramus, S. J. ; Doherty, J. A. ; Bowtell, D. D. L. ; Anglesio, M. S.

2020
AACR Philadelphia, Pa. [u.a.]

This record in other databases:  

Please use a persistent id in citations: doi:10.1158/1078-0432.CCR-20-0103

Abstract: 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 non-standardized 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.Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene-expression data from 1650 tumors. We applied resulting models to NanoString data on 3829 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.Gene-expression data was used to derive the Predictor of high-grade-serous Ovarian carcinoma molecular subTYPE (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor infiltrating lymphocytes, and outcome. The locked-down clinical-grade PrOTYPE test includes a model with 55 genes that predicted gene-expression subtype with >95% accuracy that was maintained in all analytical and biological validations.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.

Note: 2020 Oct 15;26(20):5411-5423

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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