Abstract A7: Combined copy number and expression analysis of formalin fixed-paraffin embedded (FFPE) tumours

Introduction: FFPE tissues are a valuable source of tumour material for translational research that has thus far been under-used. But progress in technology has allowed the analysis of genome wide copy number and expression changes using small amounts of degraded DNA/RNA extracted from FFPE tissues. We used two platforms: molecular inversion probes assay (MIP, Affymetrix) and c-DNA mediated Annealing Selection extension and Ligation assay (DASL, Illumina™) for analysis of RNA/DNA extracted from routine core biopsies from a clinical trial to identify molecular markers of response or resistance to chemotherapy. Method: FFPE diagnostic core biopsies of 63 patients treated with neoadjuvant adriamycin/cyclophosphamide followed by taxotere in a clinical study were used. MIP assay with 50K SNP panel was used for copy number analysis (CNA). DASL assay assessed expression of 502 genes using three probes per gene. Results: RNA and DNA of good quality were extracted from 52/63 (82%) and 46/63 (73%) core biopsy samples, respectively. Gene expression profiling was carried out using the DASL assay and there were good correlations with IHC for ER, PR and HER-2 with area under the curve of 0.95, 0.90 and 0.96 respectively, following ROC analysis for the best transcripts. Differential expression analysis between ER+ vs. ER- cancers showed that ESR1, TFF1 and LAF4 are significantly over-expressed in ER + cancers (p