The CADETSM BRAF Mutation Detection Assay

A simple free-catch urine analysis system for diagnosis and monitoring of canine transitional cell carcinoma/urothelial carcinoma- the most common form of canine bladder cancer.



Canine transitional cell carcinoma (TCC)/urothelial carcinoma (UC)

This year in the US, approximately 80,000 dogs will be diagnosed with canine transitional cell carcinoma (TCC) of the urinary tract, also known as urothelial carcinoma (UC). The disease affects the bladder, urethra, and kidneys of male and female dogs and also the prostate of males. Symptoms include straining to urinate, repeated frequent attempts to urinate, blood in the urine, and repeated bacterial infection.

TCC/UC accounts for an estimated 1-2% of all cancer cases diagnosed in dogs, and can affect any breed; however the disease shows remarkably elevated incidence in several popular breeds. These, when combined, account for over a third of all diagnosed TCC/UC cases in purebred dogs. High-risk breeds include the American Eskimo Dog, Australian Cattle Dog, Australian Shepherd, Beagle, Bichon Frise, Border Collie, Parson Russell Terrier, Lhasa Apso, Rat Terrier, Russell Terrier, Scottish Terrier, Shetland Sheepdog, West Highland White Terrier, and Wire Fox Terrier.

The traditional path to diagnosis of canine TCC/UC

Many of the symptoms of evolving TCC/UC are non-specific and shared with several other more common and/or readily treatable conditions, including cystitis and benign bladder polyps. Dogs displaying these symptoms often receive multiple rounds of antibiotic/anti-inflammatory medications over a period of weeks or months, until the lack of resolution of these symptoms triggers the consideration of other potential causes.

Accurate and timely diagnosis of TCC/UC is often challenging:

  • Conventional cytologic evaluation can be confounded by a limited sample size and difficulty in discriminating between normal and abnormal epithelial cells.
  • Small masses associated with early disease may not be evident from ultrasonography, which also lacks the ability to distinguish TCC/UC from benign bladder polyps.
  • Histopathologic evaluation of tumor biopsy is more robust, but is associated with substantial cost and potential risk.

Consequently, TCC/UC is typically diagnosed at an advanced stage, when the tumor has invaded into the underlying musculature. Thickening of the bladder wall often leads to partial or complete obstruction of the passage of urine. In 20% of cases the cancer has already metastasized by the time it is detected. These factors all indicate that current diagnostic methods have very limited ability for early detection of TCC/UC, which may in turn reduce treatment options and lead to a less favorable outcome.

Recent research offers a new DNA-based strategy for detection of TCC/UC from free-catch urine

Our research has shown that a single mutation in a gene called BRAF is present in 85% of confirmed cases of canine TCC/UC. Using state-of-the-art molecular technology, we have developed a DNA-based assay that can detect the presence of this BRAF mutation in malignant cells shed naturally into the urine of a tumor-bearing dog.

Through rigorous validation in hundreds of clinical specimens, we have shown that the mutation is not found in the urine of healthy dogs, or from dogs that have nonmalignant bladder polyps, inflammation or chronic cystitis. In cases that subsequently have undergone biopsy of a visible mass, we have also shown full concordance between the presence of a BRAF mutation in free-catch urine and subsequent pathology-based confirmation of a TCC/UC. The presence of the mutation in canine urine is therefore a highly specific indicator of the presence of a TCC/UC.

To learn more about the science behind the development of this assay click on this link to read the published study (the link will open a new tab/window)

How is the CADETSM BRAF Mutation Detection Assay utilized in a clinical setting?

The CADETSM BRAF Mutation Detection Assay  evaluates urine samples from dogs for the presence of cells harboring the BRAF mutation. The assay identifies the 85% of TCC/UC cases that are associated with the BRAF mutation.

The forensic level of detection of the assay can detect as few as 10 mutation-bearing cells in a urine sample and so is able to detect the presence of a developing TCC/UC, often several months before any advanced clinical signs associated with the cancer become evident. This enables owners and veterinarians to initiate appropriate treatment very early in the course of the disease, potentially before the mass has become invasive. Dogs already presenting with urinary symptoms that may be caused by a TCC/UC can be evaluated for the presence of a TCC/UC simply by submitting a urine sample to our testing laboratory.  Additionally, the assay offers a sensitive means to monitor BRAF-mutant TCC/UC cases during the course of their treatment, for therapeutic response and relapse.

We have developed the CADETSM BRAF Mutation Detection Assay for Diagnosis and Monitoring exclusively for veterinary professionals to utilize for expedited assessment of dogs displaying symptoms consistent with TCC/UC, and for cases undergoing treatment.

What are the key advantages offered by the CADETSM BRAF Mutation Detection Assay?

  • Convenient: The free-catch urine system is fully non-invasive, allowing specimens to be collected while the patient is at the clinic, or by the owner at home.
  • Sensitive: The assay permits forensic-level detection for earliest detection of emerging TCC/UC – even before overt symptoms of the cancer become evident.
  • Affordable: Timely detection of TCC/UC allows owners to direct their resources toward effective treatment of the cancer itself, rather than the non-specific symptoms.
  • Robust: Unlike similar tests, the CADETSM BRAF Mutation Detection Assay is not affected by the presence of blood, protein, sugars, bacteria etc in the urine.
  • Rapid: Expedited results are available in just 2-3 business days from receipt of the sample by the testing laboratory.

How can I obtain the CADETSM BRAF Mutation Detection Assay?

The CADETSM BRAF Mutation Detection Assay for Diagnosis and Monitoring is available directly to veterinary professionals through Sentinel Biomedical.

Two additional versions of the CADETSM BRAF Mutation Detection Assay are available to dog owners and breeders. These are designed as at-home tools for proactive screening of dogs for evidence of emerging TCC/UC.

  • The Annual Subscription Service Pack is available to owners and breeders through the American Kennel Club and is used to screen one dog three times over the course of one year for early evidence of TCC/UC.
  • The Breeder Service Pack is available to owners and breeders through the American Kennel Club and is used to screen multiple dogs from the same household at one time for early evidence of TCC/UC.

View this link for a comparison of all three products.

How I can learn more about the CADETSM BRAF Mutation Detection Assay for Diagnosis and Monitoring?

Please view our brochure for more information on this product.

You may also wish to view our list of Frequently Asked Questions (FAQs).