Prognostically relevant gene signatures of high-grade serous ovarian carcinoma

Roel G.W. Verhaak; Pablo Tamayo; Ji Yeon Yang; Diana Hubbard; Hailei Zhang; Chad J. Creighton; Sian Fereday; Michael Lawrence; Scott L. Carter; Craig H. Mermel; Aleksandar D. Kostic; Dariush Etemadmoghadam; Gordon Saksena; Kristian Cibulskis; Sekhar Duraisamy; Keren Levanon; Carrie Sougnez; Aviad Tsherniak; Sebastian Gomez; Robert Onofrio; Stacey Gabriel; Lynda Chin; Nianxiang Zhang; Paul T. Spellman; Yiqun Zhang; Rehan Akbani; Katherine A. Hoadley; Ari Kahn; Martin Köbel; David Huntsman; Robert A. Soslow; Anna Defazio; Michael J. Birrer; Joe W. Gray; John N. Weinstein; David D. Bowtell; Ronny Drapkin; Jill P. Mesirov; Gad Getz; Douglas A. Levine; Matthew Meyerson

doi:10.1172/JCI65833

Prognostically relevant gene signatures of high-grade serous ovarian carcinoma

Roel G.W. Verhaak, Pablo Tamayo, Ji Yeon Yang, Diana Hubbard, Hailei Zhang, Chad J. Creighton, Sian Fereday, Michael Lawrence, Scott L. Carter, Craig H. Mermel, Aleksandar D. Kostic, Dariush Etemadmoghadam, Gordon Saksena, Kristian Cibulskis, Sekhar Duraisamy, Keren Levanon, Carrie Sougnez, Aviad Tsherniak, Sebastian Gomez, Robert OnofrioStacey Gabriel, Lynda Chin, Nianxiang Zhang, Paul T. Spellman, Yiqun Zhang, Rehan Akbani, Katherine A. Hoadley, Ari Kahn, Martin Köbel, David Huntsman, Robert A. Soslow, Anna Defazio, Michael J. Birrer, Joe W. Gray, John N. Weinstein, David D. Bowtell, Ronny Drapkin, Jill P. Mesirov, Gad Getz, Douglas A. Levine, Matthew Meyerson

Molecular and Medical Genetics

Research output: Contribution to journal › Article › peer-review

454 Scopus citations

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.

Original language	English (US)
Pages (from-to)	517-525
Number of pages	9
Journal	Journal of Clinical Investigation
Volume	123
Issue number	1
DOIs	https://doi.org/10.1172/JCI65833
State	Published - Jan 2 2013

ASJC Scopus subject areas

General Medicine

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10.1172/JCI65833

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Verhaak, R. G. W., Tamayo, P., Yang, J. Y., Hubbard, D., Zhang, H., Creighton, C. J., Fereday, S., Lawrence, M., Carter, S. L., Mermel, C. H., Kostic, A. D., Etemadmoghadam, D., Saksena, G., Cibulskis, K., Duraisamy, S., Levanon, K., Sougnez, C., Tsherniak, A., Gomez, S., ... Meyerson, M. (2013). Prognostically relevant gene signatures of high-grade serous ovarian carcinoma. Journal of Clinical Investigation, 123(1), 517-525. https://doi.org/10.1172/JCI65833

Verhaak, RGW, Tamayo, P, Yang, JY, Hubbard, D, Zhang, H, Creighton, CJ, Fereday, S, Lawrence, M, Carter, SL, Mermel, CH, Kostic, AD, Etemadmoghadam, D, Saksena, G, Cibulskis, K, Duraisamy, S, Levanon, K, Sougnez, C, Tsherniak, A, Gomez, S, Onofrio, R, Gabriel, S, Chin, L, Zhang, N, Spellman, PT, Zhang, Y, Akbani, R, Hoadley, KA, Kahn, A, Köbel, M, Huntsman, D, Soslow, RA, Defazio, A, Birrer, MJ, Gray, JW, Weinstein, JN, Bowtell, DD, Drapkin, R, Mesirov, JP, Getz, G, Levine, DA & Meyerson, M 2013, 'Prognostically relevant gene signatures of high-grade serous ovarian carcinoma', Journal of Clinical Investigation, vol. 123, no. 1, pp. 517-525. https://doi.org/10.1172/JCI65833

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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.",

author = "Verhaak, {Roel G.W.} and Pablo Tamayo and Yang, {Ji Yeon} and Diana Hubbard and Hailei Zhang and Creighton, {Chad J.} and Sian Fereday and Michael Lawrence and Carter, {Scott L.} and Mermel, {Craig H.} and Kostic, {Aleksandar D.} and Dariush Etemadmoghadam and Gordon Saksena and Kristian Cibulskis and Sekhar Duraisamy and Keren Levanon and Carrie Sougnez and Aviad Tsherniak and Sebastian Gomez and Robert Onofrio and Stacey Gabriel and Lynda Chin and Nianxiang Zhang and Spellman, {Paul T.} and Yiqun Zhang and Rehan Akbani and Hoadley, {Katherine A.} and Ari Kahn and Martin K{\"o}bel and David Huntsman and Soslow, {Robert A.} and Anna Defazio and Birrer, {Michael J.} and Gray, {Joe W.} and Weinstein, {John N.} and Bowtell, {David D.} and Ronny Drapkin and Mesirov, {Jill P.} and Gad Getz and Levine, {Douglas A.} and Matthew Meyerson",

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doi = "10.1172/JCI65833",

language = "English (US)",

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T1 - Prognostically relevant gene signatures of high-grade serous ovarian carcinoma

AU - Verhaak, Roel G.W.

AU - Tamayo, Pablo

AU - Yang, Ji Yeon

AU - Hubbard, Diana

AU - Zhang, Hailei

AU - Creighton, Chad J.

AU - Fereday, Sian

AU - Lawrence, Michael

AU - Carter, Scott L.

AU - Mermel, Craig H.

AU - Kostic, Aleksandar D.

AU - Etemadmoghadam, Dariush

AU - Saksena, Gordon

AU - Cibulskis, Kristian

AU - Duraisamy, Sekhar

AU - Levanon, Keren

AU - Sougnez, Carrie

AU - Tsherniak, Aviad

AU - Gomez, Sebastian

AU - Onofrio, Robert

AU - Gabriel, Stacey

AU - Chin, Lynda

AU - Zhang, Nianxiang

AU - Spellman, Paul T.

AU - Zhang, Yiqun

AU - Akbani, Rehan

AU - Hoadley, Katherine A.

AU - Kahn, Ari

AU - Köbel, Martin

AU - Huntsman, David

AU - Soslow, Robert A.

AU - Defazio, Anna

AU - Birrer, Michael J.

AU - Gray, Joe W.

AU - Weinstein, John N.

AU - Bowtell, David D.

AU - Drapkin, Ronny

AU - Mesirov, Jill P.

AU - Getz, Gad

AU - Levine, Douglas A.

AU - Meyerson, Matthew

PY - 2013/1/2

Y1 - 2013/1/2

N2 - 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.

AB - 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.

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Prognostically relevant gene signatures of high-grade serous ovarian carcinoma

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