Sequencing of the von Hippel-Lindau gene in canine renal carcinoma.
BACKGROUND
Similarities in human and canine renal cell carcinoma (RCC) epidemiology and biologic behavior suggest that molecular mechanisms of tumorigenesis may be similar in both species. Approximately 75% of RCC in people are of the clear cell subtype, up to 85% of which are associated with mutation of the von Hippel-Lindau (VHL) gene. The canine VHL coding deoxyribonucleic acid (DNA) shares 90% identity with the human VHL gene.


OBJECTIVE
To determine whether or not RCC in dogs are associated with VHL mutations, and if so determine the prevalence, type, and location of these mutations.


METHODS
Thirteen dogs with RCC, 2 dogs with primary renal sarcomas, and 10 dogs without neoplastic kidney disease.


METHODS
DNA was extracted from paraffin-embedded RCC tissue; DNA extracts from paraffin-embedded and snap-frozen nonneoplastic canine kidneys and canine whole blood were used as negative controls. Polymerase chain reaction and sequencing of the 3 VHL exons was performed, and results compared with the accessioned canine sequence.


RESULTS
All VHL exons were amplified from 9 of 13 canine RCC samples, both renal sarcomas, 8 of 10 nonneoplastic kidney samples, and canine whole blood; only exon 2 could be amplified from 2 RCC samples. Mutations were not identified in any exons. A maximal prevalence of 33.6% for VHL mutations in canine RCC was determined.


CONCLUSIONS
Although similarities between canine and human RCC merit further investigation of the dog as a model for some subtypes of renal tumors, the lower prevalence of VHL mutations suggests that oncogenesis in these 2 species differs.
Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA. barrak@purdue.edu
B M
BM
Pressler
L E
LE
Williams
J A
JA
Ramos-Vara
K I
KI
Anderson
D000818:Animals; D001482:Base Composition; D002277:Carcinoma / Q000235:genetics / Q000662:veterinary*; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D020022:Genetic Predisposition to Disease; D007680:Kidney Neoplasms / Q000235:genetics / Q000662:veterinary*; D009154:Mutation; D012509:Sarcoma / Q000235:genetics / Q000662:veterinary; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics* / Q000378:metabolism
D051794:Von Hippel-Lindau Tumor Suppressor Protein