Epigenetic Alterations in Canine Malignant Lymphoma: Future and Clinical Outcomes

Abstract

Canine malignant lymphoma is a common neoplasia in dogs, and some studies have used dogs as a research model for molecular mechanisms of lymphomas in humans. In two species, chemotherapy is the treatment of choice, but the resistance to conventional anticancer drugs is frequent. The knowledge of molecular mechanisms of development and progression of neoplasia has expanded in recent years, and the underlying epigenetic mechanisms are increasingly well known. These studies open up new ways of discovering therapeutic biomarkers. Histone deacetylases and demethylase inhibitors could be a future treatment for canine lymphoma, and the use of microRNAs as diagnosis and prognosis biomarkers is getting closer. This review summarises the epigenetic mechanisms underlying canine lymphoma and their possible application as treatment and biomarkers, both prognostic and diagnostic.

Exploratory screening for micro-RNA biomarkers in canine multicentric lymphoma

“…Lymphoma is one of the most common occurring tumors in dogs (1)(2)(3)(4). The disease shows a prevalence of around 100 cases per 100.000 dogs and 83-85% of all canine hematopoietic neoplasias are represented by lymphoma (2,4). This tumor initiates from lymphoid cells which are B-and T-cells (4)(5)(6)(7).…”

“…The disease shows a prevalence of around 100 cases per 100.000 dogs and 83-85% of all canine hematopoietic neoplasias are represented by lymphoma (2,4). This tumor initiates from lymphoid cells which are B-and T-cells (4)(5)(6)(7). The proportions of lymphomas resulting from those cells are approximately 70% of B-cell and 30% of T-cell lymphoma (8,9).…”

“…Due to those similarities between the dog and their human counterpart, canine lymphoma is seen as a potential animal model for humans. Thus, new findings would be beneficial for both veterinary and human medicine especially concerning new diagnostic methods (1,4,5,11).…”

“…However, some few miRNAs are restricted to certain cell types (22). Although miRNAs are unable to code for proteins, they regulate gene expressions in the post-transcription process through binding in 3'UTR of target mRNA (4,22,24). Each miRNA has the ability to control hundreds of targets for almost all pathways (1,3,11,24).…”

“…However, in neoplastic cells miRNAs are dysregulated and therefore, they have an effect on the functional roles in cancer cells, such as the initiation, progression and metastasis (2, 3, 25). MicroRNAs in cancer cells are either upregulated or downregulated in comparison to healthy cells, depending on if those miRNAs act as an oncogene or tumor suppressor (1,3,4,7,22). As a matter of fact, some even have a dual-function depending on the cell type (3).…”