Institut Curie

The web supplement to
Oumou Goundiam et al. 2014


Histo-Genomic Stratification Reveals the Frequent Amplification/Overexpression of CCNE1 and BRD4 Genes in non-BRCAness Hight Grade Ovarian Carcinoma
Oumou Goundiam1 2 3 *, Pierre Gestraud4 9 10 *, Tatiana Popova5 *, Thibault De la Motte Rouge6, Virginie Fourchotte7, David Gentien3, Philippe Hupé4 9 10 11, Véronique Becette1, Claude Houdayer1 5 8, Sergio Roman-Roman3, Marc-Henri Stern1, Xavier Sastre-Garau1 2

*Equally contributed.

1Department of Biopathology, Institut Curie, Paris, France
2EA4340-BCOH, Versailles Saint-Quentin-en-Yvelines University, Guyancourt, France
3Departement of Translational Research, Institut Curie, Paris , France
4Bioinformatics and Computational Systems Biology of Cancer, Institut Curie, Paris, France
5Inserm U830, Institut Curie, Paris, France
6Departement of Medical Oncology, Institut Curie, Paris, France
7Departement of Surgery, and on behalf of the Gynecologic Study Group, Institut Curie, Paris, France
8Université Paris Descartes, Sciences Pharmaceutiques et Biologiques, Sorbonne Paris Cité, Paris, France
9Mines Paris Tech, Paris, France
10Inserm U900, Institut Curie, Paris, France
11CNRS UMR 144, Institut Curie, Paris, France


The treatment of epithelial ovarian cancer (EOC) is narrowly focused despite the heterogeneity of this disease in which outcomes remain poor. To stratify EOC patients for targeted therapy, we developed an approach integrating expression and genomic analyses including the BRCAness status. Gene expression and genomic profiling were used to identify genes recurrently (>5%) amplified and overexpressed in 105 EOC. The LST (Large-scale State Transition) genomic signature of BRCAness was applied to define molecular subgroups of EOC. Amplified/overexpressed genes clustered mainly in 3q, 8q, 19p and 19q. These changes were generally found mutually exclusive. In the 85 patients for which the genomic signature could be determined, genomic BRCAness was found in 52 cases (61.1%) and non-BRCAness in 33 (38.8%). A striking mutual exclusivity was observed between BRCAness and amplification/overexpression data. Whereas 3q and 8q alterations were preferentially observed in BRCAness EOC, most alterations on chromosome 19 were in non-BRCAness cases. CCNE1 (19q12) and BRD4 (19p13.1) amplification/overexpression was found in 19/33 (57.5%) of non-BRCAness cases. Such disequilibrium was also found in the TCGA EOC data set used for validation. Potential target genes are frequently amplified/overexpressed in non-BRCAness EOC. We report that BRD4, already identified as a target in several tumor models, is a new potential target in high grade non-BRCAness ovarian carcinoma.

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July 28 2014 13:47:07