Progress Report by University of Guelph's Ontario Veterinary College, Department of Pathobiology
microRNA analysis in dogs with lymphoma
Specific Project Objectives:
1) Determine that the microRNA profile in newly diagnosed lymphoma bearing dogs is different from healthy dogs.
2) Determine what changes in the microRNA profile occur during standard therapy, and whether the changes correlate with response to therapy and length of remission
1) Determine that the microRNA profile in newly diagnosed lymphoma bearing dogs is different from healthy dogs.
2) Determine what changes in the microRNA profile occur during standard therapy, and whether the changes correlate with response to therapy and length of remission
Objective 1We have now determined microRNA profiles from blood samples from 23 healthy dogs, 17
dogs with T cell lymphoma (a subtype of lymphoma derived from T lymphocyte cells) and 44 dogs with B cell lymphoma (a subtype of lymphoma derived from B lymphocyte cells. Using molecular biology techniques specific for canine microRNAs, we discovered overexpression of 6 different microRNAs in dogs with B cell lymphoma compared to healthy dogs, underexpression of 9 different microRNAs in dogs with B cell lymphoma compared to healthy dogs, and underexpression of 3 different microRNAs in dogs with T cell lymphoma. Furthermore, 14 microRNA were unique between tumour subtypes, and 2 in common for each tumor (that could serve as general lymphoma markers). There were also 5 microRNA present in normal healthy dogs that disappeared completely when lymphoma was present. Indeed, it seems that a panel of specific microRNAs can be used to not only confirm the diagnosis but to differentiate between the T and B cell subtypes. A poster and oral presentation have been presented at an international scientific meeting (at which CKCF was acknowledged for funding), and there will be a peer-reviewed manuscript published from this work soon (in which CKCF will be acknowledged). No outstanding lab work remaining for this objective. |
Objective 2For dogs with both T and B cell lymphoma, blood samples were assessed at weeks 0, 3, 6
and 25 during treatment for differences in expression of 40 different microRNAs. We observed several changes over time and have developed a refined panel of approximately 10 specific microRNA that correlate to successful response to therapy and length of remission period for B cell lymphoma patients. It is less clear which microRNA might have a similar use for dogs with T cell lymphoma, since we had fewer numbers of cases (T cell subtype accounts for only approximately one third of all lymphoma cases) and the biological behavior of these tumours is more variable. Part of these results have been presented at an international veterinary pathology meeting. Work remaining for this objective: We additionally wish to analyze additional samples in the period prior to relapse to determine if changes in expression of microRNA of interest start to change in blood samples before we can tell by physical examination that the dog’s cancer has returned. There are 9 dogs with each subtype of lymphoma for which we have samples in the 2-4 weeks preceding clinical relapse. |
