The Canine Health Foundation sponsored a Genetics Seminar in Saint Louis in October. This was an outstanding summary of the progress that has occurred in the last two years. The progress in the genetic study for breast cancer has been remarkable. The first gene for breast cancer has been identified in Dr. Ostrander's lab in Seattle, Washington.  Dr. Vihna's studies are very close to identifying the second gene for breast cancer. This article will summarize findings to date.

In her six month report, she stated that an autosomal dominant inheritance is highly likely. This fits very well to mode of inheritance of cancer susceptibility with mutations in various tumor suppressor genes. Therefore, we continue to think that the genes we have proposed to study are good candidates. The strategy that we had proposed to use was a linkage study. To date we have obtained information on only 80 Skyes with six affected.  While we have had good cooperation with many Skye owners and breeders, the number of cases have been very few. Therefore, I think that our study can no longer depend on the recruitment of enough cases needed for linkage studies and an alternative strategy is to be considered. We propose:

•  A) Continue to collect DNA, pedigree, histopathology and clinical course information from Skye Terriers with breast cancer
• B) Continue to evaluate the mode of inheritance that appears consistent with that of autosomal dominant, as we would expect with an inherited mutation in a genecontrolling genetic susceptibility. Therefore, we are quite encouraged with this aspect of the study.
• C) Initiate the evaluation of BRAC1, BRAC2, TP53 and AT genes for involvement in mammary carcinoma in the Skye Terrier using three new approaches.

 1.An exclusion/inclusion approach based on affected individuals. This will be feasible if we can get only several more cases, up to ten affected. The breed has historically been a long lived breed and began to notice a problem more recently, so it may be a relatively recent mutation. We will look for concordant or discordant alleles being present among the affected dogs. Another critical need is that of informative polymorphism in the candidate loci. We have developed polymorphic markers in the candidate genes [A single Nucleotide Polymorphism [T-C] in Intron 23 of the Canine BRCAI Gene]. In addition, we have amplified two more introns each of the BRCAI and BRCA2 genes  which we are screening for more polymorphic sites. We have identified positive clones for each of our candidate genes and are screening them for the presence of microsatelites. We expect to have them in place by early 2000 and be able to use them in the evaluation of the Skyes in the Spring.

2. Another useful strategy consists of a mutation the coding region of the cadidate genes.  The sequence of the coding region of the canine BRCAI and TP53 genes have been reported, but that of BRCA2 and AT are unkown. We have invested some effort in the last few months towards identification of the BRCA2 coding region, and should have this completed by the of the year.

3.In the future, if cell lines were available, we could test the effect of introducing a normal copy of a gene that we may find to be mutated in breast cancer and study the effects on the tumor. Certainly, other agents could be tested for anti-tumorogenic effects.

While this report may be very detailed, many Skye her owners have been interested in the progress to date on our project. Much has been done but much still has to be done.  Dr. Vihna does need cooperation of the Skye members to the give specimens of breast tumors or any tumors that may arise. She will do a pathological exam free of charge. She believes that we are dealing with a cluster gene, that may be responsible for several different tumors. If anyone is going to spay or neuter their Skye, she would like the specimens of testes and ovaries sent to her. Please contact Dr. Vilma at (517) 432-5140 or e-mail yuzbasyan@cym.msu.edu. Or may contact me at (843) 726-3237 or e-mail me at clandon@hargray.com.
 Don Brown, MD
Health Committee ChairmanThe Doctor's Corner