80P Expression of Hormad1, A Cancer/Testis Antigen, In Triple-Negative Breast Cancers with High Genomic Instability

Abstract

ABSTRACT Background Triple negative breast cancer (TNBC), defined by estrogen, progesterone and HER2 negativity, is a heterogeneous disease with limited targeted therapy. Molecular and immunohistochemical stratification have already identified several TNBC subgroups, characterised by different biological processes with possible implication for therapy. A clear picture of the various TNBC entities and their relationship(s), however, is still missing. Aim To shed light on this problem we have analysed a collection of 111 needle-macrodissected, clinically-annotated TNBCs using an approach based on the integration of DNA copy-number aberrations, transcriptional data and publically available gene signatures. Methods Allele-specific copy numbers adjusted for normal cell contamination were established for TNBCs, using Tumor Aberration Prediction Suite analysis on Affymetrix SNP6.0 array data. To understand how these genomic aberrations translate into the perturbation of oncogenic drivers and pathways, TNBC subgroups were further typified by using expression profiles (Affymetrix Human Exon 1.0ST), derived from the same tumour sections. Results Two distinct TNBC genomic entities characterised by significant differences in their levels of genomic instability (GI) were identified. Using a compendium of published gene signatures as reporters of specific pathway activities, revealed a striking association between the GI-high TNBC subgroup and transcriptional profiles previously associated with increased genomic instability, as well as the activation of EGFR, c-MET and immune response components. HORMAD1, a cancer/testis antigen involved in meiotic synaptonemal complex formation, was one of the classifying genes for GI-high TNBCs. Its restricted expression within a group of TNBCs was further confirmed by immunohistochemical analyses on TMAs, encompassing 222 breast carcinomas. Conclusion By integrating genomics analysis with transcriptional gene signatures we were able to establish links between different pathways and genomic instability within TNBCs, and identified HORMAD1 as a potential novel target for immunotherapy. Disclosure All authors have declared no conflicts of interest.