Patrick Devauchelle

The MTAP-CDKN2A Locus Confers Susceptibility to a Naturally Occurring Canine Cancer

Background: Advantages offered by canine population substructure, combined with clinical presentations similar to human disorders, makes the dog an attractive system for studies of cancer genetics. Cancers that have been difficult to study in human families or populations are of particular interest. Histiocytic sarcoma is a rare and poorly understood neoplasm in humans that occurs in 15% to 25% of Bernese Mountain Dogs (BMD). Methods: Genomic DNA was collected from affected and unaffected BMD in North America and Europe. Both independent and combined genome-wide association studies (GWAS) were used to identify cancer-associated loci. Fine mapping and sequencing narrowed the primary locus to a single gene region. Results: Both populations shared the same primary locus, which features a single haplotype spanning MTAP and part of CDKN2A and is present in 96% of affected BMD. The haplotype is within the region homologous to human chromosome 9p21, which has been implicated in several types of cancer. Conclusions: We present the first GWAS for histiocytic sarcoma in any species. The data identify an associated haplotype in the highly cited tumor suppressor locus near CDKN2A. These data show the power of studying distinctive malignancies in highly predisposed dog breeds. Impact: Here, we establish a naturally occurring model of cancer susceptibility due to CDKN2 dysregulation, thus providing insight about this cancer-associated, complex, and poorly understood genomic region. Cancer Epidemiol Biomarkers Prev; 21(7); 1019–27. ©2012 AACR.

In vivo model mimicking natural history of dog prostate cancer using DPC-1, a new canine prostate carcinoma cell line

Dog prostate cancer is usually considered to be highly relevant to human prostate cancer. We report the isolation of a new canine prostate cancer epithelial cell line designated DPC‐1.

Kinetics of Elimination and Acute Consequences of Cerebral Air Embolism

The pathophysiology of arterial air embolism inducing brain injuries remains unclear. Previous experiments demonstrated the usefulness of computed tomography (CT) in the detection of air emboli in canine brain. This canine study investigates CTs ability to detect small air bubbles and to determine the kinetics of air elimination from cerebral arteries and its relationship with clinical, electroencephalographic (EEG), and histological manifestations. CT detects small air embolism, and intracerebral air volume strongly correlates with injected air dose (r2 = 0.86, p = 2 × 10 3) Air clearance time significantly depends on intracerebral air volume (r2 = 0.86, p = 0 04) and on the number of bubbles (r2 = 0.71, p = 0 03), whereas half–life of air elimination does not. No relationship was found between injected air dose, air clearance time, intracerebral volume of air, and clinical, EEG, and histological findings. The data indicate that CT accurately detects small air bubbles in the early course of cerebral air embolism, that air elimination from cerebral arteries follows a first–order compartment model, and that early CT findings do not correlate with clinical, EEG, and histological manifestations.

Combined Use of Surgery and Radiation in the Treatment of an Intradural Myxoid Liposarcoma in a Dog

An intradural-extramedullary myxoid liposarcoma of the high cervical spine was diagnosed in a 9-year-old, spayed female Cavalier King Charles spaniel that was presented for a 2-month history of cervical pain and tetraparesis. Radiation therapy applied after surgery resulted in complete remission of the neurological deficits. The tumor recurred 18 months after surgical excision. A second surgery and another course of radiotherapy again resulted in complete remission of the clinical signs. The dog was euthanized 11 months after the second surgery because of tumor recurrence.

Survival times for cats with hyperthyroidism treated with a 3.35 mCi iodine-131 dose: a retrospective study of 96 cases:

Objectives Radioiodine (131I) dose determination using radiotracer kinetic studies or scoring systems, and fixed relatively high 131I dose (ie, 4 or 5 mCi) administration, are effective and associated with prolonged survival times for hyperthyroid cats. The latter method is less complicated but could expose patients and veterinary personnel to unnecessary levels of radiation. The aim of this study was to retrospectively evaluate the efficacy of a fixed 3.35 mCi 131I dose for the treatment of 96 hyperthyroid cats with no length estimation for any palpated goitre ⩾20 mm, assess outcome and identify factors associated with survival. Methods Serum total thyroxine concentrations at diagnosis and at follow-up times, survival times and cause of death were recorded. Multivariable Cox regression analysis was used to identify factors associated with time to any cause of death from 131I therapy initiation. Results Administration of a median (interquartile range) dose of 3.35 mCi (3.27–3.44 mCi) radioiodine was an effective treatment in 94/96 cats, but two cats remained hyperthyroid. No death related to hyperthyroidism was recorded. Median survival time was 3.0 years; the 1 and 2 year survival rates after 131I therapy were 90% and 78%, respectively. Low body weight (⩽3.1 kg; adjusted hazard ratio [aHR] 5.88; 95% confidence interval [CI] 2.22–16.67; P <0.01) and male gender (aHR 2.63; 95% CI 1.01–7.14; P = 0.04) were independently associated with death, whereas age, prior treatment with antithyroid drugs, reason for treatment and pretreatment azotaemia were not. Conclusions and relevance This study suggests that a fixed 3.35 mCi 131I dose treatment is effective for hyperthyroid cats with goitre(s) with a maximal length estimation <20 mm, that long-term survival can be achieved and that low body weight and male gender are significantly associated with shorter survival times.

Analyse comparée des mélanomes chez le chien et l'homme

This paper presents epidemiological and clinical data from 2350 cases of melanocytic tumours from dogs sampled in France. In addition, we present the histological and genetic characterization of subsets of melanoma cases (n=153 and n=100, respectively), with a comparative aspect to human melanomas. Dog melanomas occur at the same anatomical sites than human melanomas, but with different frequency and severity. We demonstrate that the specificities of dog melanomas make them good models to understand the non-UV pathways of human melanomas. Interestingly, somatic mutations in oral canine melanomas were detected in the NRAS and PTEN genes, precisely at the same hotspots as human mutations. In contrast, mutations in the BRAF gene were not detected. This paper highlights the similarities and differences of dog and human melanoma types and the strong potential of dog melanomas to decipher the non-UV light pathways in different melanoma types, especially mucosal and acral types.