Elucidating the transcriptional program of feline injection-site sarcoma using a cross-species approach

We report the first mRNA sequencing-based transcriptome profiling study of feline injection-site sarcoma (FISS), an aggressive iatrogenic soft-tissue malignancy. Using high-throughput short-read paired-end sequencing, we comparatively profiled FISS tumors vs. normal tissue samples as well as cultured FISS-derived cell lines vs. fibroblast-derived cells. We analyzed the mRNA-seq data to compare cancer/normal gene-level expression, identify novel FISS-specific transcripts including fusion transcripts, and identify putative somatic exonic mutations based on paired analysis of tumor and normal tissue. We compared the likelihood for genes that are differentially expressed in FISS to be orthologs of human oncogenes or tumor suppressor genes (TSGs), to the likelihood for genes that are not differentially expressed in FISS to be orthologs of human oncogenes or TSGs; this analysis showed that in FISS, there are substantial differential expression biases in feline orthologs of human oncogenes and TSGs. By averaging differential gene expression signal over ten-megabase blocks in the cat genome, we compared the FISS transcriptome to previously published patterns of somatic genomic copy number gain and loss in FISS tumors, showing substantial overlap. Finally, we compared the transcriptome profile of FISS to human and canine soft tissue sarcomas.