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  • 1.
    Giannuzzi, Diana
    et al.
    Univ Padua, Dept Comparat Biomed & Food Sci, Padua, Italy.
    Marconato, Laura
    Ctr Oncol Vet, Bologna, Italy.
    Cascione, Luciano
    USI, IOR, Bellinzona, Switzerland;SIB, Lausanne, Switzerland.
    Comazzi, Stefano
    Univ Milan, Dept Vet Med, Milan, Italy.
    Elgendy, Ramy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Pegolo, Sara
    Univ Padua, Dept Agron Food Nat Resources Anim & Environm, Padua, Italy.
    Cecchinato, Alessio
    Univ Padua, Dept Agron Food Nat Resources Anim & Environm, Padua, Italy.
    Bertoni, Francesco
    USI, IOR, Bellinzona, Switzerland.
    Aresu, Luca
    Univ Turin, Dept Vet Sci, Turin, Italy.
    Ferraresso, Serena
    Univ Padua, Dept Comparat Biomed & Food Sci, Padua, Italy.
    Mutational landscape of canine B-cell lymphoma profiled at single nucleotide resolution by RNA-seq2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 4, article id e0215154Article in journal (Refereed)
    Abstract [en]

    The genomic landscape in human B-cell lymphoma has revealed several somatic mutations and potentially relevant germline alterations affecting therapy and prognosis. Also, mutations originally described as somatic aberrations have been shown to confer cancer predisposition when occurring in the germline. The relevance of mutations in canine B-cell lymphoma is scarcely known and gene expression profiling has shown similar molecular signatures among different B-cell histotypes, suggesting other biological mechanisms underlining differences. Here, we present a highly accurate approach to identify single nucleotide variants (SNVs) in RNA-seq data obtained from 62 completely staged canine B-cell lymphomas and 11 normal B-cells used as controls. A customized variant discovery pipeline was applied and SNVs were found in tumors and differentiated for histotype. A number of known and not previously identified SNVs were significantly associated to MAPK signaling pathway, negative regulation of apoptotic process and cell death, B-cell activation, NF-kB and JAK-STAT signaling. Interestingly, no significant genetic fingerprints were found separating diffuse large B-cell lymphoma from indolent lymphomas suggesting that differences of genetic landscape are not the pivotal causative factor of indolent behavior. We also detected several variants in expressed regions of canine B-cell lymphoma and identified SNVs having a direct impact on genes. Using this brand-new approach the consequence of a gene variant is directly associated to expression. Further investigations are in progress to deeply elucidate the mechanisms by which altered genes pathways may drive lymphomagenesis and a higher number of cases is also demanded to confirm this evidence.

  • 2.
    Giannuzzi, Diana
    et al.
    Univ Padua, Dept Comparat Biomed & Food Sci, Viale Univ 16, I-35020 Padua, Italy.
    Marconato, Laura
    Ctr Oncol Vet, Bologna, Italy.
    Elgendy, Ramy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Ferraresso, Serena
    Univ Padua, Dept Comparat Biomed & Food Sci, Viale Univ 16, I-35020 Padua, Italy.
    Scarselli, Elisa
    Nouscom Srl, Rome, Italy.
    Fariselli, Piero
    Univ Padua, Dept Comparat Biomed & Food Sci, Viale Univ 16, I-35020 Padua, Italy.
    Nicosia, Alfredo
    Nouscom AG, Basel, Switzerland;Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy;CEINGE Biotecnol Avanzate Scarl, Naples, Italy.
    Pegolo, Sara
    Univ Padua, Dept Agron Food Nat Resources Anim & Environm, Padua, Italy.
    Leoni, Guido
    Nouscom Srl, Rome, Italy.
    Laganga, Paola
    Ctr Oncol Vet, Bologna, Italy.
    Leone, Vito F.
    Ctr Oncol Vet, Bologna, Italy.
    Giantin, Mery
    Univ Padua, Dept Comparat Biomed & Food Sci, Viale Univ 16, I-35020 Padua, Italy.
    Troise, Fulvia
    Nouscom Srl, Rome, Italy.
    Dacasto, Mauro
    Univ Padua, Dept Comparat Biomed & Food Sci, Viale Univ 16, I-35020 Padua, Italy.
    Aresu, Luca
    Univ Turin, Dept Vet Sci, Turin, Italy.
    Longitudinal transcriptomic and genetic landscape of radiotherapy response in canine melanoma2019In: Veterinary and Comparative Oncology, ISSN 1476-5810, E-ISSN 1476-5829, Vol. 17, no 3, p. 308-316Article in journal (Refereed)
    Abstract [en]

    Canine malignant melanoma (MM) is a highly aggressive tumour with a low survival rate and represents an ideal spontaneous model for the human counterpart. Considerable progress has been recently obtained, but the therapeutic success for canine melanoma is still challenging. Little is known about the mechanisms beyond pathogenesis and melanoma development, and the molecular response to radiotherapy has never been explored before. A faster and deeper understanding of cancer mutational processes and developing mechanisms are now possible through next generation sequencing technologies. In this study, we matched whole exome and transcriptome sequencing in four dogs affected by MM at diagnosis and at disease progression to identify possible genetic mechanisms associated with therapy failure. According to previous studies, a genetic similarity between canine MM and its human counterpart was observed. Several somatic mutations were functionally related to MAPK, PI3K/AKT and p53 signalling pathways, but located in genes other than BRAF, RAS and KIT. At disease progression, several mutations were related to therapy effects. Natural killer cell-mediated cytotoxicity and several immune-system-related pathways resulted activated opening a new scenario on the microenvironment in this tumour. In conclusion, this study suggests a potential role of the immune system associated to radiotherapy in canine melanoma, but a larger sample size associated with functional studies are needed.

  • 3.
    Iannaccone, Marco
    et al.
    Univ Teramo, Fac Biosci & Technol Food Agr & Environm, Via R Balzarini 1, I-64100 Teramo, Italy.
    Elgendy, Ramy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Univ Padua, Dept Comparat Biomed & Food Sci, Viale Univ 16, I-35020 Padua, Italy.
    Giantin, Mery
    Univ Padua, Dept Comparat Biomed & Food Sci, Viale Univ 16, I-35020 Padua, Italy.
    Martino, Camillo
    Univ Perugia, Dept Vet Med, Via S Costanzo 4, I-06126 Perugia, Italy.
    Giansante, Daniele
    Ist Zooprofilatt Sperimentale Abruzzo & Molise G, I-64100 Campo Boario, Teramo, Italy.
    Ianni, Andrea
    Univ Teramo, Fac Biosci & Technol Food Agr & Environm, Via R Balzarini 1, I-64100 Teramo, Italy.
    Dacasto, Mauro
    Univ Padua, Dept Comparat Biomed & Food Sci, Viale Univ 16, I-35020 Padua, Italy.
    Martino, Giuseppe
    Univ Teramo, Fac Biosci & Technol Food Agr & Environm, Via R Balzarini 1, I-64100 Teramo, Italy.
    RNA Sequencing-Based Whole-Transcriptome Analysis of Friesian Cattle Fed with Grape Pomace-Supplemented Diet2018In: Animals, ISSN 2076-2615, E-ISSN 2076-2615, Vol. 8, no 11, article id 188Article in journal (Refereed)
    Abstract [en]

    Grape pomace (GPO), the main by-product of the wine making process, is a rich source of polyphenols with potent antioxidant properties. Recently, GPO has emerged as a potential feed additive in livestock nutrition, with several reports describing its beneficial effects on animals' overall health status or production traits. However, little is known about it from a molecular biology standpoint. In the present study, we report the first RNA sequencing-based whole-transcriptome profiling of Friesian calves fed with a GPO-supplemented diet. We identified 367 differentially expressed genes (p < 0.05) in the GPO-supplemented calves (n = 5), when compared with unsupplemented control group (n = 5). The pathway analysis showed that cholesterol lipid biosynthesis' was the most negatively-enriched (p < 0.001) pathway in the GPO-supplemented animals. In specific terms, five important genes coding for cholesterol biosynthesis enzymes, namely the Farnesyl-diphosphate Farnesyltransferase 1 (FDFT-1), Squalene Epoxidase (SQLE), NAD(P)-dependent Steroid Dehydrogenase-like (NSDHL), Methylsterol Monooxygenase (MSMO)-1, and Sterol-C5-desaturase (SC5D), two major transcription factors (the Sterol Regulatory Element-binding Transcription Factor 1 and 2), as well as the Low-Density Lipoprotein Receptor (LDLR), were all downregulated following GPO supplementation. Such an effect was mirrored by a reduction of blood cholesterol levels (p = 0.07) and a lowered (p < 0.001) Malondialdehyde (lipid oxidation marker) level in carcasses. We provide evidence on the effects of GPO-supplemented diets on the whole-transcriptome signature in veal calves, which mainly reflects an antioxidant activity.

  • 4.
    Zorzan, Eleonora
    et al.
    Univ Padua, Dept Comparat Biomed & Food Sci, Padua, Italy.
    Elgendy, Ramy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Univ Padua, Dept Comparat Biomed & Food Sci, Padua, Italy.
    Giantin, Mery
    Univ Padua, Dept Comparat Biomed & Food Sci, Padua, Italy.
    Dacasto, Mauro
    Univ Padua, Dept Comparat Biomed & Food Sci, Padua, Italy.
    Sissi, Claudia
    Univ Padua, Dept Pharmaceut & Pharmacol Sci, Padua, Italy.
    Whole-Transcriptome Profiling of Canine and Human in Vitro Models Exposed to a G-Quadruplex Binding Small Molecule2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 17107Article in journal (Refereed)
    Abstract [en]

    G-quadruplexes (G4) are secondary nucleic acid structures that have been associated with genomic instability and cancer progression. When present in the promoter of some oncogenes, G4 structures can affect gene regulation and, hence, represent a possible therapeutic target. In this study, RNA-Seq was used to explore the effect of a G4-binding anthraquinone derivative, named AQ1, on the whole-transcriptome profiles of two common cell models for the study of KIT pathways; the human mast cell leukemia (HMC1.2) and the canine mast cell tumor (C2). The highest non-cytotoxic dose of AQ1 (2 mu M) resulted in 5441 and 1201 differentially expressed genes in the HMC1.2 and C2 cells, respectively. In both cell lines, major pathways such as cell cycle progression, KIT- and MYC-related pathways were negatively enriched in the AQ1-treated group, while other pathways such as p53, apoptosis and hypoxia-related were positively enriched. These findings suggest that AQ1 treatment induces a similar functional response in the human and canine cell models, and provide news insights into using dogs as a reliable translational model for studying G4-binding compounds.

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