Premium
Histo‐genomic stratification reveals the frequent amplification/overexpression of CCNE 1 and BRD 4 genes in non‐BRCAness high grade ovarian carcinoma
Author(s) -
Goundiam Oumou,
Gestraud Pierre,
Popova Tatiana,
De la Motte Rouge Thibault,
Fourchotte Virginie,
Gentien David,
Hupé Philippe,
Becette Véronique,
Houdayer Claude,
RomanRoman Sergio,
Stern MarcHenri,
SastreGarau Xavier
Publication year - 2015
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29568
Subject(s) - biology , gene , gene expression profiling , gene duplication , genetics , cancer research , microbiology and biotechnology , gene expression
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.