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Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE).
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.
Afiliação
  • Talhouk A; British Columbia's Gynecological Cancer Research Program (OVCARE), BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, British Columbia, Canada.
  • George J; University of British Columbia, Department of Obstetrics and Gynecology, Vancouver, British Columbia, Canada.
  • Wang C; The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.
  • Budden T; Mayo Clinic, Division of Biomedical Statistics and Informatics, Department of Health Science Research, Rochester, Minnesota.
  • Tan TZ; University of NSW Sydney, School of Women's and Children's Health, Faculty of Medicine, Sydney, New South Wales, Australia.
  • Chiu DS; The University of Manchester, CRUK Manchester Institute, Manchester, United Kingdom.
  • Kommoss S; National University of Singapore, Cancer Science Institute of Singapore, Center for Translational Medicine, Singapore, Singapore.
  • Leong HS; British Columbia's Gynecological Cancer Research Program (OVCARE), BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, British Columbia, Canada.
  • Chen S; Tuebingen University Hospital, Department of Women's Health, Tuebingen, Germany.
  • Intermaggio MP; Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
  • Gilks B; Cedars-Sinai Medical Center, Center for Cancer Prevention and Translational Genomics, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
  • Nazeran TM; University of NSW Sydney, School of Women's and Children's Health, Faculty of Medicine, Sydney, New South Wales, Australia.
  • Volchek M; British Columbia's Gynecological Cancer Research Program (OVCARE), BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, British Columbia, Canada.
  • Elatre W; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
  • Bentley RC; British Columbia's Gynecological Cancer Research Program (OVCARE), BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, British Columbia, Canada.
  • Senz J; Royal Women's Hospital, Anatomical Pathology, Parkville, Victoria, Australia.
  • Lum A; Department of Pathology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Chow V; Department of Pathology, Duke University Hospital, Durham, North Carolina.
  • Sudderuddin H; British Columbia's Gynecological Cancer Research Program (OVCARE), BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, British Columbia, Canada.
  • Mackenzie R; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
  • Leong SCY; British Columbia's Gynecological Cancer Research Program (OVCARE), BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, British Columbia, Canada.
  • Liu G; British Columbia's Gynecological Cancer Research Program (OVCARE), BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, British Columbia, Canada.
  • Johnson D; British Columbia's Gynecological Cancer Research Program (OVCARE), BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, British Columbia, Canada.
  • Chen B; British Columbia's Gynecological Cancer Research Program (OVCARE), BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, British Columbia, Canada.
  • Group A; British Columbia's Gynecological Cancer Research Program (OVCARE), BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, British Columbia, Canada.
  • Alsop J; British Columbia's Gynecological Cancer Research Program (OVCARE), BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, British Columbia, Canada.
  • Banerjee SN; British Columbia's Gynecological Cancer Research Program (OVCARE), BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, British Columbia, Canada.
  • Behrens S; British Columbia's Gynecological Cancer Research Program (OVCARE), BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, British Columbia, Canada.
  • Bodelon C; Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
  • Brand AH; QIMR Berghofer Medical Research Institute, Department of Genetics and Computational Biology, Brisbane, Queensland, Australia.
  • Brinton L; Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia.
  • Carney ME; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
  • Chiew YE; The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Gynaecology Unit, London, United Kingdom.
  • Cushing-Haugen KL; German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany.
  • Cybulski C; NCI, Division of Cancer Epidemiology and Genetics, Bethesda, Maryland.
  • Ennis D; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.
  • Fereday S; NCI, Division of Cancer Epidemiology and Genetics, Bethesda, Maryland.
  • Fortner RT; Department of Obstetrics and Gynecology, University of Hawaii, John A. Burns School of Medicine, Honolulu, Hawaii.
  • García-Donas J; Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia.
  • Gentry-Maharaj A; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.
  • Glasspool R; Fred Hutchinson Cancer Research Center, Program in Epidemiology, Division of Public Health Sciences, Seattle, Washington.
  • Goranova T; Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
  • Greene CS; Imperial College London, Division of Cancer and Ovarian Cancer Action Research Centre, Department Surgery & Cancer, London, United Kingdom.
  • Haluska P; Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.
  • Harris HR; Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
  • Hendley J; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
  • Hernandez BY; German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany.
  • Herpel E; HM Hospitales Centro Integral Oncológico Clara Campal (HM CIOCC), Madrid, Spain.
  • Jimenez-Linan M; University College London, MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London, United Kingdom.
  • Karpinskyj C; Department of Medical Oncology, Beatson West of Scotland Cancer Centre and University of Glasgow, Glasgow, United Kingdom.
Clin Cancer Res ; 26(20): 5411-5423, 2020 10 15.
Article em En | MEDLINE | ID: mdl-32554541
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 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 analytic and biological validations.

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.See related commentary by McMullen et al., p. 5271.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Cistadenoma Seroso / Transcriptoma / Proteínas de Neoplasias Idioma: En Ano de publicação: 2020 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Cistadenoma Seroso / Transcriptoma / Proteínas de Neoplasias Idioma: En Ano de publicação: 2020 Tipo de documento: Article