Simultaneous Inactivation of the &lt;i&gt;p16, p15&lt;/i&gt; and &lt;i&gt;p14&lt;/i&gt; Genes Encoding Cyclin-Dependent Kinase Inhibitors in Canine T-Lymphoid Tumor Cells

Fujiwara‐Igarashi, Aki; Goto‐Koshino, Yuko; Mochizuki, Hiroyasu; Maeda, Shingo; Fujino, Yasuhito; Ohno, Koichi; Tsujimoto, Hajime

doi:10.1292/jvms.12-0351

Cited by 12 publications

(6 citation statements)

References 45 publications

(85 reference statements)

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“…Primers for canine p16 have been described, based on a design within the third exon, but these do not distinguish any residual DNA in samples. 41 The results of qRT-PCR were comparable with those of microarray but across a greater dynamic range and only within the six dogs used. An exception was p53, which was downregulated substantially in stimulated samples when compared to microarray data.…”

Section: Discussionmentioning

confidence: 69%

Cluster Analysis of Tumor Suppressor Genes in Canine Leukocytes Identifies Activation State

Daly

Mortlock

Taylor

et al. 2015

Bioinform Biol Insights

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Cells of the immune system undergo activation and subsequent proliferation in the normal course of an immune response. Infrequently, the molecular and cellular events that underlie the mechanisms of proliferation are dysregulated and may lead to oncogenesis, leading to tumor formation. The most common forms of immunological cancers are lymphomas, which in dogs account for 8%–20% of all cancers, affecting up to 1.2% of the dog population. Key genes involved in negatively regulating proliferation of lymphocytes include a group classified as tumor suppressor genes (TSGs). These genes are also known to be associated with progression of lymphoma in humans, mice, and dogs and are potential candidates for pathological grading and diagnosis. The aim of the present study was to analyze TSG profiles in stimulated leukocytes from dogs to identify genes that discriminate an activated phenotype. A total of 554 TSGs and three gene set collections were analyzed from microarray data. Cluster analysis of three subsets of genes discriminated between stimulated and unstimulated cells. These included 20 most upregulated and downregulated TSGs, TSG in hallmark gene sets significantly enriched in active cells, and a selection of candidate TSGs, p15 (CDKN2B), p18 (CDKN2C), p19 (CDKN1A), p21 (CDKN2A), p27 (CDKN1B), and p53 (TP53) in the third set. Analysis of two subsets suggested that these genes or a subset of these genes may be used as a specialized PCR set for additional analysis.

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Section: Discussionmentioning

confidence: 69%

Cluster Analysis of Tumor Suppressor Genes in Canine Leukocytes Identifies Activation State

Daly

Mortlock

Taylor

et al. 2015

Bioinform Biol Insights

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“…Clustering of lymphoma in related dogs has been reported, suggesting an inherited predisposition . Genetic and epigenetic changes have been identified in canine lymphoma, but the studies generally have been across multiple breeds . Studies within a breed have identified germline changes across tumor types, potentially supporting a breed‐associated cancer risk that is not specific for lymphoma …”

Section: Discussionmentioning

confidence: 99%

Demographic risk factors for lymphoma in Australian dogs: 6201 cases

Bennett

Taylor

Williamson

2018

Veterinary Internal Medicne

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BackgroundLymphoma is common in the dog. Studies of population risk factors primarily have been derived from referral institution or insurance data.ObjectiveTo identify and quantify the host risk factors for lymphoma in a broad population of Australian dogs.AnimalsData on 6201 client owned dogs were retrieved from a commercial veterinary laboratory, a general practice group and 2 referral hospitals.MethodsData collected included breed, sex, and neuter status. A reference population of 640 105 dogs was generated from the referral hospitals and from council registration data. The risk of lymphoma by sex and neuter status was calculated as odds ratios (OR).ResultsThe study identified 30 breeds at increased risk of lymphoma, 15 that have not been reported previously, and 26 breeds at decreased risk, 18 that have not been reported previously. Males were over represented compared to females with an OR of 1.1 (95% CI, 1.1–1.2; P < .001). Neutered animals were at higher risk compared to intact animals with an OR of 3.2 (95% CI, 2.9–3.5) which was found in both males (OR, 2.8; 95% CI; 2.5–3.2) and females (OR, 4.4; 95% CI, 3.5–5.1).Conclusions and Clinical ImportanceBreed, sex, and neuter status alter the risk of lymphoma in dogs. These 3 factors must be considered when evaluating lymphoma risk as potential markers of underlying differences in disease etiology. Comparison of breeds at increased and decreased risk could be advantageous when evaluating specific etiological factors.

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“…Mutations in the tumor suppressor gene p53 are relatively rare in cL (Veldhoen et al 1998;Tomiyasu et al 2010) and although p53 expression is typically absent or of low intensity (Sueiro et al 2004;Sokolowska et al 2005), expression appears more common in older animals, high grade, and possibly T-cell lymphomas (Sueiro et al 2004). Increased Rb (retinoblastoma) phosphorylation and subsequent activation of CDK4, is common in high-grade canine T-cell lymphoma and might result from deletion of p16/loss of dog chromosome 11 (Fosmire et al 2007), hypermethylation of the CpG island of the p16 gene (Fujiwara-Igarashi et al 2014), and possibly from a deletion of the p15Àp14Àp16 locus (Fujiwara-Igarashi et al 2013). Increased Rb phosphorylation in high-grade canine B-cell lymphoma appears to correlate with c-Myc overexpression and trisomy of dog chromosome 13 (Fosmire et al 2007).…”

Section: Molecular Biology Of Canine Lymphomamentioning

confidence: 99%

Canine lymphoma: a review

Zandvliet

2016

Veterinary Quarterly

160

206

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Canine lymphoma (cL) is a common type of neoplasia in dogs with an estimated incidence rate of 20-100 cases per 100,000 dogs and is in many respects comparable to non-Hodgkin lymphoma in humans. Although the exact cause is unknown, environmental factors and genetic susceptibility are thought to play an important role. cL is not a single disease, and a wide variation in clinical presentations and histological subtypes is recognized. Despite this potential variation, most dogs present with generalized lymphadenopathy (multicentric form) and intermediate to high-grade lymphoma, more commonly of B-cell origin. The most common paraneoplastic sign is hypercalcemia that is associated with the T-cell immunophenotype. Chemotherapy is the treatment of choice and a doxorubicin-based multidrug protocol is currently the standard of care. A complete remission is obtained for most dogs and lasts for a median period of 7-10 months, resulting in a median survival of 10-14 months. Many prognostic factors have been reported, but stage, immunophenotype, tumor grade, and response to chemotherapy appear of particular importance. Failure to respond to chemotherapy suggests drug resistance, which can be partly attributed to the expression of drug transporters of the ABC-transporter superfamily, including P-gp and BCRP. Ultimately, most lymphomas will become drug resistant and the development of treatments aimed at reversing drug resistance or alternative treatment modalities (e.g. immunotherapy and targeted therapy) are of major importance. This review aims to summarize the relevant data on cL, as well as to provide an update of the recent literature.

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Simultaneous Inactivation of the <i>p16, p15</i> and <i>p14</i> Genes Encoding Cyclin-Dependent Kinase Inhibitors in Canine T-Lymphoid Tumor Cells

Cited by 12 publications

References 45 publications

Cluster Analysis of Tumor Suppressor Genes in Canine Leukocytes Identifies Activation State

Cluster Analysis of Tumor Suppressor Genes in Canine Leukocytes Identifies Activation State

Demographic risk factors for lymphoma in Australian dogs: 6201 cases

Canine lymphoma: a review

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