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Longitudinal transcriptomic and genetic landscape of radiotherapy response in canine melanoma
Univ Padua, Dept Comparat Biomed & Food Sci, Viale Univ 16, I-35020 Padua, Italy.ORCID iD: 0000-0003-2975-0385
Ctr Oncol Vet, Bologna, Italy.ORCID iD: 0000-0002-7843-615X
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.ORCID iD: 0000-0002-2592-3448
Univ Padua, Dept Comparat Biomed & Food Sci, Viale Univ 16, I-35020 Padua, Italy.
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2019 (English)In: Veterinary and Comparative Oncology, ISSN 1476-5810, E-ISSN 1476-5829, Vol. 17, no 3, p. 308-316Article in journal (Refereed) Published
Abstract [en]

Canine malignant melanoma (MM) is a highly aggressive tumour with a low survival rate and represents an ideal spontaneous model for the human counterpart. Considerable progress has been recently obtained, but the therapeutic success for canine melanoma is still challenging. Little is known about the mechanisms beyond pathogenesis and melanoma development, and the molecular response to radiotherapy has never been explored before. A faster and deeper understanding of cancer mutational processes and developing mechanisms are now possible through next generation sequencing technologies. In this study, we matched whole exome and transcriptome sequencing in four dogs affected by MM at diagnosis and at disease progression to identify possible genetic mechanisms associated with therapy failure. According to previous studies, a genetic similarity between canine MM and its human counterpart was observed. Several somatic mutations were functionally related to MAPK, PI3K/AKT and p53 signalling pathways, but located in genes other than BRAF, RAS and KIT. At disease progression, several mutations were related to therapy effects. Natural killer cell-mediated cytotoxicity and several immune-system-related pathways resulted activated opening a new scenario on the microenvironment in this tumour. In conclusion, this study suggests a potential role of the immune system associated to radiotherapy in canine melanoma, but a larger sample size associated with functional studies are needed.

Place, publisher, year, edition, pages
WILEY , 2019. Vol. 17, no 3, p. 308-316
Keywords [en]
dog, exome sequencing, melanoma, radiation therapy, RNA-seq
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-393646DOI: 10.1111/vco.12473ISI: 000480308000011PubMedID: 30805995OAI: oai:DiVA.org:uu-393646DiVA, id: diva2:1354755
Available from: 2019-09-26 Created: 2019-09-26 Last updated: 2019-09-26Bibliographically approved

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