Title

Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE).

Authors

Aline Talhouk
Joshy George, The Jackson LaboratoryFollow
Chen Wang
Timothy Budden
Tuan Zea Tan
Derek S Chiu
Stefan Kommoss
Huei San Leong
Stephanie Chen
Maria P Intermaggio
Blake Gilks
Tayyebeh M Nazeran
Mila Volchek
Wafaa Elatre
Rex C Bentley
Janine Senz
Amy Lum
Veronica Chow
Hanwei Sudderuddin
Robertson Mackenzie
Samuel C Y Leong
Geyi Liu
Dustin Johnson
Billy Chen
Aocs Group
Jennifer Alsop
Susana N Banerjee
Sabine Behrens
Clara Bodelon
Alison H Brand
Louise Brinton
Michael E Carney
Yoke-Eng Chiew
Kara L Cushing-Haugen
Cezary Cybulski
Darren Ennis
Sian Fereday
Renée T Fortner
Jesús García-Donas
Aleksandra Gentry-Maharaj
Rosalind Glasspool
Teodora Goranova
Casey S Greene
Paul Haluska
Holly R Harris
Joy Hendley
Brenda Y Hernandez
Esther Herpel
Mercedes Jimenez-Linan
Chloe Karpinskyj
Scott H Kaufmann
Gary L Keeney
Catherine J Kennedy
Martin Köbel
Jennifer M Koziak
Melissa C Larson
Jenny Lester
Liz-Anne Lewsley
Jolanta Lissowska
Jan Lubiński
Hugh Luk
Geoff Macintyre
Sven Mahner
Iain A McNeish
Janusz Menkiszak
Nikilyn Nevins
Ana Osorio
Oleg Oszurek
José Palacios
Samantha Hinsley
Celeste L Pearce
Malcolm C Pike
Anna M Piskorz
Isabelle Ray-Coquard
Valerie Rhenius
Cristina Rodriguez-Antona
Raghwa Sharma
Mark E Sherman
Dilrini De Silva
Naveena Singh
Peter Sinn
Dennis Slamon
Honglin Song
Helen Steed
Euan A Stronach
Pamela J Thompson
Aleksandra Tołoczko
Britton Trabert
Nadia Traficante
Chiu-Chen Tseng
Martin Widschwendter
Lynne R Wilkens
Stacey J Winham
Boris Winterhoff
Alicia Beeghly-Fadiel
Javier Benitez
Andrew Berchuck
James D Brenton
Robert Brown
Jenny Chang-Claude
Georgia Chenevix-Trench
Anna deFazio
Peter A Fasching
María J García
Simon A Gayther
Marc T Goodman
Jacek Gronwald
Michelle J Henderson
Beth Y Karlan
Linda E Kelemen
Usha Menon
Sandra Orsulic
Paul D P Pharoah
Nicolas Wentzensen
Anna H Wu
Joellen M Schildkraut
Mary Anne Rossing
Gottfried E Konecny
David G Huntsman
Ruby Yun-Ju Huang
Ellen L Goode
Susan J Ramus
Jennifer A Doherty
David D Bowtell
Michael S Anglesio

Document Type

Article

Publication Date

10-15-2020

Keywords

JGM, JAXCC

JAX Source

Clin Cancer Res 2020 Oct 15; 26(20):5411-5423

PMID

32554541

DOI

https://doi.org/10.1158/1078-0432.ccr-20-0103

Abstract

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.

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