79P Identification of A Brcaness Signature in Triple Negative Breast Cancer by Comparative Genomic Hybridization

Abstract

ABSTRACT Background Triple Negative Breast Cancers (TNBC) that represent 12% to 20% of total Breast Cancer (BC), have a worse outcome compared with other breast cancer subtypes. TNBC often show a deficiency in DNA double strand break repair mechanisms. This deficiency is generally related to inactivation of a repair enzymatic complex involving BRCA caused either by genetic mutations, epigenetic modifications, or by post-transcriptional regulations via miRNA. The identification of BC presenting a DNA double strand break repair deficiency could be useful to select patients that should get the best benefit from PARP inhibitors therapy. In this study, we have identified by Comparative Genomic Hybridization array (CGH-array) a recurrent gain characteristic of BRCA1 mutated tumours. Methods 135 formalin-fixed paraffin embedded (FFPE) tumours including TNBC (BRCA1 mutated and non-mutated), LumA, LumB and Her2-neu amplified BC were obtained from a local tumour collection. DNA was extracted and genomic copy-number alterations were analysed by CGH-array (Agilent, SuperPrint G3 Human CGH 8x60K Oligo Microarrays). Results In this study, we have identified by CGH-array a genomic region amplified in 90 % of the BRCA1 mutated tumours (29/32). A FISH assay on sections from FFPE samples was developed and confirmed the CGH profile. The identification of relevant genes whose expression is up-regulated within the recurrently gained region is underway. Conclusions The CGH profile and FISH assay developed in this study could allow the rapid identification of BRCAness breast tumours, improving the diagnostic performance and orienting the selection of the appropriate therapy. The up-regulated genes themselves might also represent potential therapeutic targets Acknowledgements This work was supported by Plan National Cancer, Belgium, action 29. Disclosure All authors have declared no conflicts of interest.