title: A multicancer-like syndrome in a dog characterized by p53 and cell cycle-checkpoint kinase 2 (CHK2) mutations and sirtuin gene (SIRT1) down-regulation.
abstract: BACKGROUND
  We have investigated SIRT1, p53 and cell cycle-checkpoint kinase 2 (CHK2) gene dysfunction in a dog with a multicancer syndrome-like in order to evaluate their potential role in the determinism of the disease and to establish a possible correlation between SIRT1 transcript level and p53 expression status.
  
  
  METHODS
  Blood sample and tumour samples from a pure breed English Setter dog with different tumours were used for this study. Nucleotide sequence analysis was performed with a DNA autosequencer in order to examine p53 and CHK2 mutations. In addition, the expression level of SIRT1 was quantified by Southern Blot analysis of Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR).
  
  
  RESULTS
  Cytological examination revealed five different tumours: a cutaneous sebaceous epithelioma, a cutaneous mast cell tumour, a testicular Sertoli cell tumour, an oral malignant melanoma, and a cutaneous squamous cell carcinoma. Sequencing analysis revealed the presence of a nucleotide substitution, (CGG>CAG) exon 7 of the p53 gene in DNA from peripheral blood mononuclear cells (PBMCs) as well as in the melanoma; whereas the other four cancers showed the loss of the wild-type allele. Furthermore, CHK2 mutation at codon 311 has been identified in the melanoma and sebaceous epithelioma. In addition, SIRT1 cDNA expression decreased in all tumour samples compared to cDNA SIRT1expression level in peripheral blood mononuclear cells (PBMCs) in the same dog.
  
  
  CONCLUSIONS
  These results suggest that the germ line mutation of the p53 gene at codon 248 might be, at least, one cause of the multicancer syndrome-like in our dog; furthermore, we show a possible correlation between SIRT1 transcript level and p53 mutations status. The regulatory role of SIRT1 in tumour suppressor pathways suggests that the net effect seen may represent both direct and indirect downstream regulation and it is likely to depend on the presence or absence of functional p53.
authors: Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Rome, Italy. gabriellamarfe@libero.it
authors: G
authors: G
authors: Marfe
authors: L
authors: L
authors: De Martino
authors: M
authors: M
authors: Tafani
authors: M
authors: M
authors: Irno-Consalvo
authors: M P
authors: MP
authors: Pasolini
authors: L
authors: L
authors: Navas
authors: S
authors: S
authors: Papparella
authors: A
authors: A
authors: Gambacurta
authors: O
authors: O
authors: Paciello
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D015139:Blotting, Southern / Q000662:veterinary; D004283:Dog Diseases / Q000235:genetics* / Q000473:pathology; D004285:Dogs; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D007573:Jaw Neoplasms / Q000235:genetics / Q000473:pathology / Q000662:veterinary; D008297:Male; D009378:Neoplasms, Multiple Primary / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D056564:Sirtuin 1 / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology / Q000662:veterinary; D013577:Syndrome
chemical_list: D017346:Protein Serine-Threonine Kinases; D056564:Sirtuin 1