In vivo model for mastocytosis: A comparative review

Ranieri, Girolamo; Marech, Ilaria; Pantaleo, Maria Abbondanza; Piccinno, M.; Roncetti, M.; Mutinati, Maddalena; Rizzo, Annalisa; Gadaleta, Cosmo Damiano; Introna, Marcello; Patruno, Rosa; Sciorsci, Raffaele Luigi

doi:10.1016/j.critrevonc.2014.10.010

Cited by 10 publications

(9 citation statements)

References 99 publications

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“…Moreover, comparative oncology studies show that some canine and human cancers share similar genetic aberrations, including chromosomal instability, common cytogenetic aberrations, involvement of identical oncogenes or tumor suppressors, and even identical somatic mutations (5). The identification of such driver genetic alterations, both in dogs and humans, is highly informative for the development of dedicated new targeted therapies, such as the development of c-kit inhibitors for canine mast cell disorders (6). Among such driver events, we focused on translocations that generally lead to overexpression of oncogenes.…”

Section: Introductionmentioning

confidence: 99%

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Discovery of Human-Similar Gene Fusions in Canine Cancers

et al. 2017

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Canine cancers represent a tremendous natural resource due to their incidence and striking similarities to human cancers, sharing similar clinical and pathologic features as well as oncogenic events, including identical somatic mutations. Considering the importance of gene fusions as driver alterations, we explored their relevance in canine cancers. We focused on three distinct human-comparable canine cancers representing different tissues and embryonic origins. Through RNA-Seq, we discovered similar gene fusions as those found in their human counterparts: - in B-cell lymphoma, - in glioma, and - in dermatofibrosarcoma protuberans-like. We showed not only similar partner genes but also identical breakpoints leading to oncogene overexpression. This study demonstrates similar gene fusion partners and mechanisms in human-dog corresponding tumors and allows for selection of targeted therapies in preclinical and clinical trials with pet dogs prior to human trials, within the framework of personalized medicine. .

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Section: Introductionmentioning

confidence: 99%

“…5 Institut Bergoni e, Bordeaux, France. 6 D epartement de Pathologie Cellulaire et Tissulaire, CHU, Angers, France. 7 APHP, Hopital Saint-Louis, Hemato-oncologie; Universit e Paris Diderot, Sorbonne Paris Cit e, Paris, France.…”

Section: Introductionmentioning

confidence: 99%

Discovery of Human-Similar Gene Fusions in Canine Cancers

et al. 2017

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“…CMCT shares many phenotypic and molecular characteristics with mastocytosis, including paraclinical and clinical manifestations, and a high prevalence of activating C-KIT mutations [ 7 , 8 ]. CMCT in dogs thus provides a good naturally occurring comparative disease model for studying mastocytosis [ 9 , 10 ]. As reported in humans [ 1 , 11 , 12 ], there is evidence for germ-line risk factors in dogs as specific breeds, including golden retrievers, Labrador retrievers, boxers and Chinese shar-pei, have a high frequency of CMCT [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Association Study of Golden Retrievers Identifies Germ-Line Risk Factors Predisposing to Mast Cell Tumours

et al. 2015

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Canine mast cell tumours (CMCT) are one of the most common skin tumours in dogs with a major impact on canine health. Certain breeds have a higher risk of developing mast cell tumours, suggesting that underlying predisposing germ-line genetic factors play a role in the development of this disease. The genetic risk factors are largely unknown, although somatic mutations in the oncogene C-KIT have been detected in a proportion of CMCT, making CMCT a comparative model for mastocytosis in humans where C-KIT mutations are frequent. We have performed a genome wide association study in golden retrievers from two continents and identified separate regions in the genome associated with risk of CMCT in the two populations. Sequence capture of associated regions and subsequent fine mapping in a larger cohort of dogs identified a SNP associated with development of CMCT in the GNAI2 gene (p = 2.2x10-16), introducing an alternative splice form of this gene resulting in a truncated protein. In addition, disease associated haplotypes harbouring the hyaluronidase genes HYAL1, HYAL2 and HYAL3 on cfa20 and HYAL4, SPAM1 and HYALP1 on cfa14 were identified as separate risk factors in European and US golden retrievers, respectively, suggesting that turnover of hyaluronan plays an important role in the development of CMCT.

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“…Mast cells (MCs) neoplastic disorders occur in both canine and human species sharing many but not all biological and clinical features. Spontaneous MCT has been proposed as a model to study biological and therapeutic approach for human neoplastic MCs diseases, i. e. mastocytosis [ 28 ]. At the same time, due to the implications of c-KIT aberrations in the development of MCs tumors, canine MCT could represent a useful model to study human c-KIT driven malignancies and TKIs, targeting c-kit.…”

Section: Discussionmentioning

confidence: 99%

Mutational Hotspot of TET2, IDH1, IDH2, SRSF2, SF3B1, KRAS, and NRAS from Human Systemic Mastocytosis Are Not Conserved in Canine Mast Cell Tumors

et al. 2015

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IntroductionBoth canine cutaneous mast cell tumor (MCT) and human systemic mastocytosis (SM) are characterized by abnormal proliferation and accumulation of mast cells in tissues and, frequently, by the presence of activating mutations in the receptor tyrosine kinase V-Kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog (c-KIT), albeit at different incidence (>80% in SM and 10–30% in MCT). In the last few years, it has been discovered that additional mutations in other genes belonging to the methylation system, the splicing machinery and cell signaling, contribute, with c-KIT, to SM pathogenesis and/or phenotype. In the present study, the mutational profile of the Tet methylcytosine dioxygenase 2 (TET2), the isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2), the serine/arginine-rich splicing factor 2 (SRSF2), the splicing factor 3b subunit 1 (SF3B1), the Kirsten rat sarcoma viral oncogene homolog (KRAS) and the neuroblastoma RAS viral oncogene homolog (NRAS), commonly mutated in human myeloid malignancies and mastocytosis, was investigated in canine MCTs.MethodsUsing the Sanger sequencing method, a cohort of 75 DNA samples extracted from MCT biopsies already investigated for c-KIT mutations were screened for the “human-like” hot spot mutations of listed genes.ResultsNo mutations were ever identified except for TET2 even if with low frequency (2.7%). In contrast to what is observed in human TET2 no frame-shift mutations were found in MCT samples.ConclusionResults obtained in this preliminary study are suggestive of a substantial difference between human SM and canine MCT if we consider some target genes known to be involved in the pathogenesis of human SM.

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In vivo model for mastocytosis: A comparative review

Cited by 10 publications

References 99 publications

Discovery of Human-Similar Gene Fusions in Canine Cancers

Discovery of Human-Similar Gene Fusions in Canine Cancers

Genome-Wide Association Study of Golden Retrievers Identifies Germ-Line Risk Factors Predisposing to Mast Cell Tumours

Mutational Hotspot of TET2, IDH1, IDH2, SRSF2, SF3B1, KRAS, and NRAS from Human Systemic Mastocytosis Are Not Conserved in Canine Mast Cell Tumors

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