A31
Identification of differentially expressed sense and antisense transcript pairs in breast epithelial tissues
Anita Grigoriadis1, Gavin Oliver2, Austin Tanner2, Howard Kendrick3, Matt Smalley3, Parmjit Jat4, A.Munro Neville1
1Ludwig Institute for Cancer Research, London, UK, 2Almac Diagnostics, Northern Ireland, UK, 3The Breakthrough Breast Cancer Research Centre, London, UK, 4Institute of Neurology, London, UK
More than 20% of human transcripts have naturally occurring antisense products (or natural antisense transcripts - NATs), some of which may play a key role in a range of human diseases. To date, several databases of in silico-defined human sense–antisense (SAS) pairs have appeared; however differentially expressed SAS pairs in breast tissue have not yet been interrogated. We, therefore, investigated the expression levels of antisense and sense transcripts in a pool of normal luminal cells and malignant human breast tumours substantially enriched for epithelial cells using the Affymetrix HG-U133 Plus 2.0 and Almac Diagnostics Breast Cancer DSA™ microarray technologies as well as Massively Parallel Signature Sequencing expression data. Out of 2500 antisense transcripts identified by DSA™ platform 431 NATswere confirmed by either of the other two technologies. Within this validated set, 257 had a corresponding sense transcript and 163 SAS transcripts of such pairs have not been previously reported.. When the differential expression levels between the normal and the malignant breast samples for these SAS pairs were determined, a positive correlation of most of them was observed. Quantitative PCR of selected SAS pairs in a panel of breast cancer cell lines and solid breast tumours not only confirmed their expression in the breast tissues, but furthermore identified cell type specific differences in SAS expression levels. Further studies will determine whether these differences in SAS transcript levels translate to their functional involvement in breast cancer.
