Introduction

Epigenetic dysregulation of gene expression in cancer provides a valuable perspective to explain cancer biology and predict novel therapeutic opportunities. Conventional genomic techniques have failed to identify recurrent genetic alterations in complex veterinary cancers, like hemangiosarcoma. The Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) profiles regions of the genome accessible to transcription factor binding and gene transcription providing a snapshot of epigenetic alterations in cancer. The goal of this pilot study is to profile epigenetic changes in splenic hemangiosarcoma and benign splenic tumors using ATAC-seq.

Methods

Samples were collected via an ongoing 400 dog prospective clinical trial of canine splenic hemangiosarcoma (Ethos-PUSH). ATAC-seq has been performed on >2 distinct tumor regions with matched normal splenic samples from 7 tumors (4 hemangiosarcoma, 2 nodular hyperplasia/hematomas, 1 splenic marginal zone lymphoma). Histopathology of all tumor and normal samples was performed by a single pathologist to confirm diagnosis and tumor content.

Results

Benign hematomas/nodular hyperplasia and hemangiosarcoma share open chromatin patterns, while marginal zone lymphoma has a distinct chromatin pattern. Furthermore, matched normal samples share open chromatin patterns with adjacent tumor samples despite lacking evidence of neoplasia on histopathology.

Conclusion

Preliminary results suggest dogs who develop benign hematoma/nodular hyperplasia and hemangiosarcoma have a shared spleen-wide epigenetic signature. This signature suggests a common epigenetic event that fosters neoplastic transformation of endothelial precursor cells in benign and malignant neoplasms and implicates epigenetic targeting drugs could be useful in modulating tumor microenvironment and treating canine splenic hemangiosarcoma.

Funding Information

Ethos Veterinary Health and Scacheri Lab.