Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.

<h4>Objective</h4>Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate simi...

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Autores principales:	Jenny-Maria Jönsson, Ida Johansson, Mev Dominguez-Valentin, Siker Kimbung, Mats Jönsson, Jesper Hansen Bonde, Päivi Kannisto, Anna Måsbäck, Susanne Malander, Mef Nilbert, Ingrid Hedenfalk
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/85eda4e688ad494cb2cbd74e0846e38d
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spelling	oai:doaj.org-article:85eda4e688ad494cb2cbd74e0846e38d2021-11-25T06:00:25ZMolecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.1932-620310.1371/journal.pone.0107643https://doaj.org/article/85eda4e688ad494cb2cbd74e0846e38d2014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0107643https://doaj.org/toc/1932-6203<h4>Objective</h4>Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer.<h4>Methods</h4>Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset.<h4>Results</h4>5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged.<h4>Conclusions</h4>These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast cancer, and suggest that biomarkers and targeted therapies may overlap between these tumor subsets. The link between benign and borderline ovarian cancer and luminal breast cancer may indicate endocrine responsiveness in a subset of ovarian cancers.Jenny-Maria JönssonIda JohanssonMev Dominguez-ValentinSiker KimbungMats JönssonJesper Hansen BondePäivi KannistoAnna MåsbäckSusanne MalanderMef NilbertIngrid HedenfalkPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e107643 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jenny-Maria Jönsson Ida Johansson Mev Dominguez-Valentin Siker Kimbung Mats Jönsson Jesper Hansen Bonde Päivi Kannisto Anna Måsbäck Susanne Malander Mef Nilbert Ingrid Hedenfalk Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.
description	<h4>Objective</h4>Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer.<h4>Methods</h4>Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset.<h4>Results</h4>5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged.<h4>Conclusions</h4>These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast cancer, and suggest that biomarkers and targeted therapies may overlap between these tumor subsets. The link between benign and borderline ovarian cancer and luminal breast cancer may indicate endocrine responsiveness in a subset of ovarian cancers.
format	article
author	Jenny-Maria Jönsson Ida Johansson Mev Dominguez-Valentin Siker Kimbung Mats Jönsson Jesper Hansen Bonde Päivi Kannisto Anna Måsbäck Susanne Malander Mef Nilbert Ingrid Hedenfalk
author_facet	Jenny-Maria Jönsson Ida Johansson Mev Dominguez-Valentin Siker Kimbung Mats Jönsson Jesper Hansen Bonde Päivi Kannisto Anna Måsbäck Susanne Malander Mef Nilbert Ingrid Hedenfalk
author_sort	Jenny-Maria Jönsson
title	Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.
title_short	Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.
title_full	Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.
title_fullStr	Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.
title_full_unstemmed	Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.
title_sort	molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/85eda4e688ad494cb2cbd74e0846e38d
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Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.

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