Longitudinal transcriptomic and genetic landscape of radiotherapy response in canine melanoma.
Vet Comp Oncol
; 17(3): 308-316, 2019 Sep.
Article
en En
| MEDLINE
| ID: mdl-30805995
ABSTRACT
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Enfermedades de los Perros
/
Transcriptoma
/
Melanoma
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Vet Comp Oncol
Asunto de la revista:
MEDICINA VETERINARIA
/
NEOPLASIAS
Año:
2019
Tipo del documento:
Article
País de afiliación:
Italia