Abstract LB-403: Recurrent fusion transcripts in breast cancer

Abstract

Abstract Breast cancer is the second leading cause of cancer deaths among women in the United States. Genome wide analyses in primary breast tumors and ∼50 breast cancer cell lines using gene expression profiling revealed subsets defined as luminal, basal-like, ERBB2 and claudin-low. The general hypothesis is that recurrent fusion transcripts exist and play a central role in the pathophysiology and clinical outcome of breast cancer. We identified recurrent fusion transcripts specific to breast cancer cell lines by performing Solexa based paired-end sequencing of whole-transcriptome (RNAseq) using 9 basal, 9 luminals, 4 ERBB2 and 1 claudin-low breast cancer cell lines. In addition, we cross-compared the predicted fusion transcripts with that of copy number and gene expression changes in the respective cell lines and performed gene ontology (GO) based enrichment analysis using the genes that were involved in the fusion. The sequencing of 19 breast cancer cell lines resulted in a range of ∼15 million to ∼45 million paired-end reads of 76 bp per cell line and out of which 93% to 98.6% had quality reads. On average, we predicted ∼14 fusion genes per cell lines (331 fusion genes in total) that are expressed atleast in one cell line. Interestingly, basal breast cancer cell lines on average have more number of fusion transcripts (∼13 per cell line and 115 in total) whereas luminal cell lines have only ∼9 predicted fusion transcripts per cell line (84 in total). Among the 418 unique genes that were involved in fusion processes, 20% of the genes occurred atleast twice and GO enrichment analysis show similar terms to be significantly enriched. Intriguingly, we identified 24 different recurrent fusion transcripts in total. In summary, the data demonstrates that there is more number of predicted fusion transcripts in breast cancer than initially thought. Also, the data suggest that genes with similar functions or processes fuse together. Currently studies are in progress to test if recurrent gene fusions may have a functional role, which may assist in the design of appropriate strategies to target recurrent events, and may be associated with poor outcome of basal breast cancers. Overall, this may improve the prognosis of breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-403. doi:1538-7445.AM2012-LB-403