[251] Integrative Analysis of Papillary Carcinomas of the Breast

Daniel Nava Rodrigues, Paul Wilkerson, Raphaelle Duprez, Alan Mackay, Maryou B Lambros, Arnaud Gauthier, Odette Mariani, Marthe Mansour, Rachael Natrajan, Britta Weigelt, Anne Vincent-Salomon, Jorge S Reis-Filho. The Institute of Cancer Research, London, United Kingdom; Institut Curie, Paris, France; Cancer Research UK London Research Institute, London, United Kingdom

Background: Papillary carcinoma (PC) is a rare histological special type of breast cancer associated with a relatively good prognosis. Three morphological variants of PC (encapsulated (EPC), solid (SPC), and invasive (IPC)) are currently recognised. Few studies to date have investigated the repertoire of genomic alterations of papillary carcinomas. The aims of this study were (i) to identify recurrent copy number aberrations in PCs, (ii) to identify genes that are consistently overexpressed when amplified in PCs, and (iii) to determine whether the three morphological subtypes of PC are characterised by distinct copy number or gene expression profiles.
Design: Twenty-two frozen PCs of the breast (10 EPCs, 6 IPCs, 5 SPCs, and 1 mixed EPC-SPC) were subjected to Affymetrix SNP6 genotyping and gene expression profiling using the Illumina HT12 platform. Hierarchical clustering was performed using categorical copy number states and gene expression data to identify subgroups of PCs. Supervised analysis of the different histological variants of papillary carcinomas was performed. SNP6 copy number and gene expression data were overlaid to determine genes whose expression is regulated by gene copy number aberrations.
Results: PCs displayed the genomic aberrations found in oestrogen receptor (ER)-positive breast cancers of low histological grade, including gains of 1q, 8q, 16p, and 20q, and losses of 8p, 11q and 16q. Recurrent amplifications mapping to 8p12-p11, 11q13, and 20q13 were observed. Hierarchical cluster analysis of the gene expression data revealed a cluster significantly enriched for EPCs. Significance analysis of microarrays identified seven genes significantly differentially expressed between EPCs and non-EPCs (i.e. NFKBIZ, ERP27, H2AFY2, ARHGDIB, YPEL2, INADL and GBP3). Overlay of SNP6 copy number and gene expression data identified 3899 genes whose expression was copy number regulated. Functional annotation of these genes revealed a significant enrichment for genes playing a role in the PI3K/AKT/mTOR and oestrogen receptor signalling pathways. Furthermore, 6 genes were found to be overexpressed when amplified, all mapping to the 11q13 amplicon (i.e. CCND1, ORAOV1, FADD, PPFIA1, CTTN and SHANK2).
Conclusions: Papillary breast carcinomas have genomic aberrations consistent with those reported for ER-positive invasive ductal carcinomas of no special type. Integration of gene copy number and gene expression data revealed that activation of the PI3K/AKT/mTOR pathway may be driven by genomic aberrations in these cancers.
Category: Breast

Monday, March 19, 2012 1:00 PM

Poster Session II # 74, Monday Afternoon

 

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