Canine_Mast_Cell_Tumours___Arendt-sc-5145
Canine_Mast_Cell_Tumours___Arendt
Canine mast cell tumours are one of the most common cancers in dogs. Despite this, our ability to understand the behaviour of this tumour and accurately detect evidence of metastasis is limited. As mast cells secrete a large amount of cytokines and have surface receptors for these substances, mast cell tumours can attract other mast cells. Mast cells can be found in low numbers in body tissues and cavities. Currently there is no way of determining if a mast cell is neoplastic and moving away from a mast cell tumour to metastasize or if it is reactive and moving towards the mast cell tumour, stimulated by cytokines. Studies have investigated the value of clinical staging of dogs affected by mast cell tumours, however the concern is that sometimes, reactive mast cells are diagnosed as metastatic spread or that metastatic mast cells are misinterpreted as normal. In human mastocytosis somatic mutations are commonly found in the KIT (KITD816V present in 75% of patients), TET2, JAK-2, ASXL1 and CBL genes among others.  Exome sequencing of tumour and paired normal samples is an efficient way of evaluating somatic driver mutations. In this study we will perform exome sequencing on mast cell tumour tissue, matched peripheral blood from the same individual and mast cell clusters from histologically confirmed lymph node metastasis from a subset of individuals. From this we hope to be able to find driver mutations in mast cell tumours and to evaluate if the same cell population is present in the lymph node. Matched peripheral blood will be used to filter out normal germline variations. The purpose of these screens is to develop better diagnostic screening methods for diagnosis and confirmation of metastasis as well as promoting the utility of the dog as a comparative cancer model.
Canine mast cell tumours are one of the most common cancers in dogs. Despite this, our ability to understand the behaviour of this tumour and accurately detect evidence of metastasis is limited. As mast cells secrete a large amount of cytokines and have surface receptors for these substances, mast cell tumours can attract other mast cells. Mast cells can be found in low numbers in body tissues and cavities. Currently there is no way of determining if a mast cell is neoplastic and moving away from a mast cell tumour to metastasize or if it is reactive and moving towards the mast cell tumour, stimulated by cytokines. Studies have investigated the value of clinical staging of dogs affected by mast cell tumours, however the concern is that sometimes, reactive mast cells are diagnosed as metastatic spread or that metastatic mast cells are misinterpreted as normal. In human mastocytosis somatic mutations are commonly found in the KIT (KITD816V present in 75% of patients), TET2, JAK-2, ASXL1 and CBL genes among others.  Exome sequencing of tumour and paired normal samples is an efficient way of evaluating somatic driver mutations. In this study we will perform exome sequencing on mast cell tumour tissue, matched peripheral blood from the same individual and mast cell clusters from histologically confirmed lymph node metastasis from a subset of individuals. From this we hope to be able to find driver mutations in mast cell tumours and to evaluate if the same cell population is present in the lymph node. Matched peripheral blood will be used to filter out normal germline variations. The purpose of these screens is to develop better diagnostic screening methods for diagnosis and confirmation of metastasis as well as promoting the utility of the dog as a comparative cancer model.