Molecular and immunohistochemical subtyping of canine lymphoma

Smith, Patrick (2021) Molecular and immunohistochemical subtyping of canine lymphoma. MVM(R) thesis, University of Glasgow.

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Abstract

Lymphoma is a broad term for a diverse group of neoplastic diseases of lymphocytes. In human oncology precise lymphoma subclassification, often based on immunohistochemistry (IHC) and molecular genetic abnormalities, allows accurate prognostication and treatment. Currently in canine oncology such precise subclassification is not possible. As a result, the prognosis and treatment of canine lymphoma is less tailored to a patient’s specific disease. This study has two parts, each aimed at improving our ability to subclassify canine lymphomas. The first part involved investigating novel IHC stains in a group of canine lymphoma samples to identify their staining characteristics, with a focus on canine T-cell lymphomas (cTCL). The second investigated the prevalence and characteristics of TRAF3 mutations in a group of canine B-cell lymphomas (cBCL) and assessed cTCL and non-lymphoma samples to see if TRAF3 mutations are specific to cBCL.

For IHC investigation, 46 cTCL and 13 cBCL samples were assessed using c-Kit, CD30 and clusterin. Five, three and 11 cases were positive for c-Kit, CD30 and clusterin respectively. Three cases of cBCL were positive for clusterin and none were positive for either CD30 or c-Kit.

For TRAF3 investigation, 49 dogs were included (n= 24 cBCL; n= 25 non-cBCL). Eleven dogs had matched non-tumour DNA assessed to determine if mutations were germline or somatic. All dogs had TRAF3 assessed by Sanger sequencing. The prevalence of deleterious TRAF3 mutations in cBCL was 36%. A deleterious TRAF3 mutation was suspected to be germline in 1/5 cases with matched non-tumour DNA available for comparison. Deleterious mutations were not found in specimens from the non-cBCL group. Several synonymous variants were identified in cBCL and non-cBCL samples, which likely represent polymorphisms. These results indicate TRAF3 mutations are common in cBC and may be important in the pathogenesis of cBCL.

These investigations have used novel IHC markers and TRAF3 analysis to characterise a broad group of canine lymphomas. Further investigation is needed to investigate if these characterisations are useful in prognosticating or directing treatment in dogs with lymphoma.

Item Type: Thesis (MVM(R))
Qualification Level: Masters
Subjects: S Agriculture > SF Animal culture > SF600 Veterinary Medicine
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Supervisor's Name: Morris, Professor Joanna and Waugh, Elspeth
Date of Award: 2021
Depositing User: Theses Team
Unique ID: glathesis:2021-82384
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 13 Aug 2021 08:39
Last Modified: 13 Aug 2021 11:29
Thesis DOI: 10.5525/gla.thesis.82384
URI: http://theses.gla.ac.uk/id/eprint/82384
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