The Role of Complex Translocations Associated with TP53 Somatic Mutations for Aiding Prognosis of Canine Diffuse Large B cell Lymphoma
Lymphoma accounts for up to 24% of all cancers diagnosed in pet dogs. Among these cases diffuse large B-cell lymphoma (DLBCL) is the most common subtype. Despite continued advances in veterinary medicine, the response to treatment for canine lymphoma remains highly variable with no reliable means to predict response.
Studies of lymphoma in people have identified characteristic genome changes that have both diagnostic and prognostic significance. In human DLBCL, mutations in the TP53 gene, and genome rearrangements involving the MYC, BCL2 and BCL6 genes have been shown to confer particularly poor prognosis in cases treated with standard of care multi-agent (CHOP-based) chemotherapy.
The investigator’s previous CHF-funded studies have shown that canine cancers, including lymphoma, exhibit genomic changes that are conserved with those observed in the corresponding human cancers, and have identified MYC and BCL2 rearrangements and a high frequency of TP53 mutation in canine DLBCL.
This research will screen a well-defined collection of over 450 pre-treatment, canine DLBCL samples to determine accurate frequencies of these genome changes. The researchers will investigate the correlation of these target aberrations with duration of first remission, and identify key genomic signatures that may aid prognosis of prospective canine lymphoma cases.
The data generated should assist owners and veterinarians with decisions regarding treatment with CHOP. Patients with signatures predictive of poor response to conventional CHOP chemotherapy may benefit from more aggressive treatment at the outset to improve outcome.
Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02317
Dr. Matthew Breen, PhD
North Carolina State University