01052-A: Whole Genome Association Mapping of Squamous Cell Carcinoma (SCC) of the Digit in the Standard Poodle

Grant Amount: $12,000

Elaine A Ostrander, PhD; National Human Genome Research Institute

January 1, 2008 - December 31, 2008

Sponsor(s):

Breed(s): Standard Poodle

Research Program Area: Oncology

Project Summary

Squamous cell carcinoma (SCC) of the digit is a highly breed specific skin cancer with increased risk found in large black dogs, including the standard poodle, giant schnauzer and Gordon setter. This cancer is more aggressive than most SCCs with 80% of cases involving bone lysis and 5-13% recurring in multiple toes. When invasive, the cancer metastasizes to the lung or lymph nodes and ultimately leads to mortality. The disease occurs in older dogs and therefore it is not possible to control through selective breeding. We proposed a whole genome association study to identify the locus and eventually the gene(s) responsible for increased susceptibility to SCC of the digit. An ACORN grant of 12K was received to allow us to begin our studies. Using the Affymetrix whole genome SNP chip, we proposed to scan the genomes of at least 40 affected and 40 unaffected black standard poodles to determine where similarities and differences in sequence lie, in order to find regions of the genome likely to contain the disease gene. Chromosomal regions showing significant association with the disease will undergo follow-up analyses with fine mapping. Within any genomic region identified by such a study are likely to be several genes. Selecting the genes to study intensely for a mutation is based on several criteria including the function of the gene, specifically it�s likelihood of playing a role in cancer. To date we have scanned about half the planned number of cases and controls and identified a single major peak under which an excellent candidate gene lies. The peak is large, however, and spans about 500-800 kb of genome DNA. We would like to reduce the size under the peak, and thus reduce the workload associated with scanning candidate genes by looking at other blacked coated breeds with the same disease, such as the Giant Schnauzer and Gordon Setter. Sample collection in those breeds has been relatively successful and analysis of Giant Schnauzer data appears to confirm the locus, although it does not make it smaller. We are currently awaiting funds from the grant to continue our scan of the additional poodle samples we have collected in hand as well as the Gordon Setter samples. A deeper scan is needed to determine if other loci are involved and to determine if the preliminary result, obtained with a very small number of dogs, is replicated and achieves statistical significance. In the meantime, we have followed up our initial results and screening the one candidate gene by direct DNA sequencing. No mutations have been found to date, but the region is only 50% screened.

Publication(s)