Predictive value of p16 or Rb inactivation in a model of naturally occurring canine non-Hodgkin's lymphoma

We report here the use of naturally occurring non-Hodgkin's lymphoma (NHL) as a model to investigate heritable risk and predictive factors for response in this disease. Dogs are at risk to

develop virtually all subtypes of sporadic NHL seen in humans (no transforming lymphotropic viruses such as Epstein–Barr virus or human T-cell leukemia virus type 1 have been conclusively

identified in dogs); these tumors not only have morphological similarities between both species, but they also share a similar natural history and clinical behavior1, 2, 3 (Table 1). NHL is

the most common life-threatening cancer of dogs, accounting for up to 24% of all malignancies and over 80% of all hematopoietic cancers.1 Untreated cases, especially those of high-grade

type, rarely survive beyond 3 months after diagnosis, but the disease is generally responsive to standard of care using CHOP-based chemotherapy protocols, increasing both the length and

quality of affected dogs' lives.1 With standard of care, remission can be achieved in >85% of canine NHL cases, and median survival ranges between 9 and 12 months.4, 5 This represents

approximately 10% of an average canine lifetime, thus providing a fair target to compare the outcome between dogs and people. Predictive factors for survival in dogs include immunophenotype,

clinical substage and histologic subtype. However, as is true for NHL in humans, additional criteria are required to generate more refined schemes that can accurately predict outcomes.

Beyond these similarities, peculiar properties of canine NHL increase its value as a model for the human disease. Specifically, the age-adjusted incidence of NHL (excluding other lymphoid

neoplasms) is estimated at 107 per 100 000 dog-years,6 a rate approximately five times higher than that reported for humans by the SEER program (∼22 per 100 000).7 In addition, the relative

risk for this disease in some breeds is up to four times higher than the average for all dogs,6, 8, 9 suggesting that heritable risk factors for the disease have been firmly established in

the derivation of specific breeds.

This work was supported by grants from the American Cancer Society, the AKC Canine Health Foundation and the Starlight Fund.

University of Colorado Health Sciences Center, Denver, CO, USA

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