Roberta Ferrari, Laura Marconato, Patrizia Boracchi, Damiano Stefanello, Francesco Godizzi, Daniela Murgia, Valentina Schievenin, Maria Amati, Eugenio Faroni, Paola Roccabianca
{"title":"Splenic stromal sarcomas in dogs: Outcome and clinicopathological prognostic factors in 32 cases.","authors":"Roberta Ferrari, Laura Marconato, Patrizia Boracchi, Damiano Stefanello, Francesco Godizzi, Daniela Murgia, Valentina Schievenin, Maria Amati, Eugenio Faroni, Paola Roccabianca","doi":"10.1111/vco.12941","DOIUrl":"10.1111/vco.12941","url":null,"abstract":"<p><p>Due to the low frequency and the changes in diagnostic techniques and terminology during the last few years, only little clinical information is available on splenic stromal sarcoma (SSS). This multi-institutional study aimed at gathering clinical cases of SSS in dogs and investigates their clinical behaviour, as well as analyse possible clinicopathological prognostic factors, including the use of adjuvant therapy. Dogs with a histologically confirmed SSS that underwent splenectomy were retrospectively included. To be included in the study, either FFPE tissue blocks or multiple tissue sections had to be available for histopathologic and immunohistochemical revision. Clinical and pathological variables, along with adjuvant therapy data, were collected. Cumulative incidence of metastatic disease was analysed through univariate and bivariate analyses. The impact of adjuvant chemotherapy on metastasis incidence and survival was assessed, considering an estimated propensity score. A total of 32 dogs were included. Among them, 22 developed metastases with an incidence of 37.5%, 59.38%, and 65.94% at 6, 12, and 24 months, respectively. Univariate analysis identified mitotic count, total scoring, and necrosis as prognostic factors. In bivariate analysis, mitotic count remained prognostic. The administration of adjuvant chemotherapy did not have an impact on metastasis incidence or survival time. The study found that dogs with SSSs are at high risk of metastasis, although a small subgroup may experience longer survival after splenectomy. Mitotic count was the only variable having a reliable prognostic impact. Adjuvant chemotherapy did not appear to decrease the incidence of metastasis or prolong survival in these dogs.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"12-21"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sharadha Sakthikumar, Manisha Warrier, Derick Whitley, Salvatore Facista, Jonathan Adkins, Sara Aman, Darwin Tsinajinnie, Natalie Duran, Giulia Siravegna, Zeeshan Ahmed, Kenneth Day, Brooklyn Jenkins, Nidhi Patel, Kirk Ryden, Joe Nadai, Kathryn Banovich, Barbara Powers, Jeffrey Edwards, Jennifer Steinberg, Susan Fielder, Shukmei Wong, Sara A Byron, Tyler Izatt, Victoria Zismann, Martin Boateng, Zhanyang Zhu, Han-Yu Chuang, Jeffrey M Trent, David Haworth, Esther Chon, William Hendricks, Guannan Wang
{"title":"Genomic analysis across 53 canine cancer types reveals novel mutations and high clinical actionability potential.","authors":"Sharadha Sakthikumar, Manisha Warrier, Derick Whitley, Salvatore Facista, Jonathan Adkins, Sara Aman, Darwin Tsinajinnie, Natalie Duran, Giulia Siravegna, Zeeshan Ahmed, Kenneth Day, Brooklyn Jenkins, Nidhi Patel, Kirk Ryden, Joe Nadai, Kathryn Banovich, Barbara Powers, Jeffrey Edwards, Jennifer Steinberg, Susan Fielder, Shukmei Wong, Sara A Byron, Tyler Izatt, Victoria Zismann, Martin Boateng, Zhanyang Zhu, Han-Yu Chuang, Jeffrey M Trent, David Haworth, Esther Chon, William Hendricks, Guannan Wang","doi":"10.1111/vco.12944","DOIUrl":"10.1111/vco.12944","url":null,"abstract":"<p><p>A genomic understanding of the oncogenic processes and individual variability of human cancer has steadily fueled improvement in patient outcomes over the past 20 years. Mutations within tumour tissues are routinely assessed through clinical genomic diagnostic assays by academic and commercial laboratories to facilitate diagnosis, prognosis and effective treatment stratification. The application of genomics has unveiled a wealth of mutation-based biomarkers in canine cancers, suggesting that the transformative principles that have revolutionized human cancer medicine can be brought to bear in veterinary oncology. To advance clinical genomics and genomics-guided medicine in canine oncology, we have developed and validated a canine cancer next-generation sequencing gene panel for the identification of multiple mutation types in clinical specimens. With this panel, we examined the genomic landscapes of 828 tumours from 813 dogs, spanning 53 cancer types. We identified 7856 alterations, encompassing copy number variants, single nucleotide variants, indels and internal tandem duplications. Additionally, we evaluated the clinical utility of these alterations by incorporating a biomarker framework from comprehensive curation of primary canine literature and inferences from human cancer genomic biomarker literature and clinical diagnostics. Remarkably, nearly 90% of the cases exhibited mutations with diagnostic, prognostic or therapeutic implications. Our work represents a thorough assessment of genomic landscapes in a large cohort of canine cancers, the first of its kind for its comprehensive inclusion of multiple mutation types and structured annotation of biomarkers, demonstrating the clinical potential of leveraging mutation-based biomarkers in veterinary oncology.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"30-41"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xue Zhang, Chen Mei, Zhixuan Liang, Yan Zhi, Haojun Xu, Hongjun Wang, Hong Dong
{"title":"Homoharringtonine induces apoptosis of mammary carcinoma cells by inhibiting the AKT/mTOR signaling pathway.","authors":"Xue Zhang, Chen Mei, Zhixuan Liang, Yan Zhi, Haojun Xu, Hongjun Wang, Hong Dong","doi":"10.1111/vco.12948","DOIUrl":"10.1111/vco.12948","url":null,"abstract":"<p><p>Mammary tumour is the most common type of tumour in dogs, especially in unneutered female dogs. Homoharringtonine (HHT) is a natural alkaloid that can be used to treat various types of human tumour. However, the inhibitory effect and mechanism of HHT on canine mammary carcinomas (CMC) remain unclear. This study aimed to evaluate the inhibitory effect of HHT on CMC in vitro and determine its underlying molecular mechanism. The effects of HHT on the cytotoxicity of CMC U27 cells were evaluated by the cell counting kit-8, wound healing, and Transwell assays. HHT-induced apoptosis of U27 cells was detected by JC-1 and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. Moreover, the gene expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were analysed using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and the protein expression of protein kinase B/mammalian target of rapamycin (AKT/mTOR) and mitochondrial apoptosis proteins were determined by western blotting. Furthermore, mammary tumour-bearing mouse models were established using 4T1 cells to evaluate the therapeutic effect of HHT. It was found that HHT could significantly down-regulated the protein expression of p-AKT, p-mTOR, and Bcl-2, and up-regulated the protein expression of P53, Bax, cleaved caspase-3, and cleaved caspase-9. In addition, HHT significantly suppressed both tumour volume and mass in mammary tumour mice. In conclusion, HHT damages CMC cells by inhibiting the AKT/mTOR signalling pathway and inducing mitochondrial apoptosis. Such findings lay a theoretical foundation for the clinical treatment of CMC and provide more options for clinical medication.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"57-69"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138800012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Abstracts from the ESVONC Annual Congress, 22-27 May 2023.","authors":"","doi":"10.1111/vco.12951","DOIUrl":"10.1111/vco.12951","url":null,"abstract":"","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":"22 Suppl 1 ","pages":"3-19"},"PeriodicalIF":2.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139672769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic trial of fluvastatin in a cell line xenograft model of canine mammary gland cancer.","authors":"Mohamed Issam Atmane, Anne-Laurence Vigneau, Francis Beaudry, Charlène Rico, Derek Boerboom, Marilène Paquet","doi":"10.1111/vco.12926","DOIUrl":"10.1111/vco.12926","url":null,"abstract":"<p><p>The Hippo signalling pathway is involved in breast cancer and canine mammary tumour (CMT). This study sought to evaluate the efficacy of fluvastatin on the Hippo pathway and its main effectors, YAP and TAZ, in vivo in a murine CMT cell line xenograft model. On treatment day 1, mice were divided into four groups: vehicle, fluvastatin, doxorubicin or a combination therapy. Tumour volumes were monitored with callipers and tissues harvested on day 28th of treatment. Histopathological examination of tumour tissues and major organs was performed as well as tumour evaluation of necrosis, apoptosis, cellular proliferation, expression of YAP, TAZ and the mRNA levels of four of their target genes (CTGF, CYR61, ANKRD1 and RHAMM2). Results showed a statistically significant variation in tumour volumes only for the combination therapy and final tumour weight only for the doxorubicin group compared to control. There was no significant difference in tumour necrosis, expression of CC3, ki-67, YAP and TAZ measured by immunohistochemistry and in the mRNA levels of the target genes. Unexpectedly, lung metastases were found in the control group (9) and not in the fluvastatin treated group (7). In addition, mass spectrometry-based quantification of fluvastatin reveals concentrations comparable to levels reported to exert therapeutic effects. This study shows that fluvastatin tumours concentration reached therapeutic levels without having an effect on the hippo pathway or various tumour parameters. Interestingly, only the control group had lung metastases. This study is the first to explore the repurposing of statins for cancer treatment in veterinary medicine.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"634-645"},"PeriodicalIF":2.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10234220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K J Nytko, M S Weyland, S Dressel-Böhm, S Scheidegger, L Salvermoser, C Werner, S Stangl, A C Carpinteiro, B Alkotub, G Multhoff, S Bodis, C Rohrer Bley
{"title":"Extracellular heat shock protein 70 levels in tumour-bearing dogs and cats treated with radiation therapy and hyperthermia.","authors":"K J Nytko, M S Weyland, S Dressel-Böhm, S Scheidegger, L Salvermoser, C Werner, S Stangl, A C Carpinteiro, B Alkotub, G Multhoff, S Bodis, C Rohrer Bley","doi":"10.1111/vco.12923","DOIUrl":"10.1111/vco.12923","url":null,"abstract":"<p><p>Hyperthermia is a form of a cancer treatment which is frequently applied in combination with radiotherapy (RT) to improve therapy responses and radiosensitivity. The mode of action of hyperthermia is multifactorial; the one hand by altering the amount of the blood circulation in the treated tissue, on the other hand by modulating molecular pathways involved in cell survival processes and immunogenic interactions. One of the most dominant proteins induced by hyperthermia is the major stress-inducible heat shock protein 70 (Hsp70). Hsp70 can be found in the blood either as a free-protein (free HSP70) derived from necrotic cells, or lipid-bound (liposomal Hsp70) when it is actively released in extracellular vesicles (EVs) by living cells. The aim of the study was to evaluate the levels of free and liposomal Hsp70 before and after treatment with RT alone or hyperthermia combined with radiotherapy (HTRT) in dogs and cats to evaluate therapy responses. Peripheral blood was collected from feline and canine patients before and at 2, 4, 6 and 24 h after treatment with RT or HTRT. Hsp70 enzyme-linked immunosorbent assays (ELISAs) were performed to determine the free and liposomal Hsp70 concentrations in the serum. The levels were analysed after the first fraction of radiation to study immediate effects and after all applied fractions to study cumulative effects. The levels of free and liposomal Hsp70 levels in the circulation were not affected by the first singular treatment and cumulative effects of RT in cats however, after finalizing all treatment cycles with HTRT free and liposomal Hsp70 levels significantly increased. In dogs, HTRT, but not treatment with RT alone, significantly affected liposomal Hsp70 levels during the first fraction. Free Hsp70 levels were significantly increased after RT, but not HTRT, during the first fraction in dogs. In dogs, on the other hand, RT alone resulted in a significant increase in liposomal Hsp70, but HTRT did not significantly affect the liposomal Hsp70 when cumulative effects were analysed. Free Hsp70 was significantly induced in dogs after both, RT and HTRT when cumulative effects were analysed. RT and HTRT treatments differentially affect the levels of free and liposomal Hsp70 in dogs and cats. Both forms of Hsp70 could potentially be further investigated as potential liquid biopsy markers to study responses to RT and HTRT treatment in companion animals.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"605-615"},"PeriodicalIF":2.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10129094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The second-generation curcumin analogue RL71 elicits G2/M cell cycle arrest and apoptosis in canine osteosarcoma cells.","authors":"Barnaby Kelly, Douglas Thamm, Rhonda J Rosengren","doi":"10.1111/vco.12922","DOIUrl":"10.1111/vco.12922","url":null,"abstract":"<p><p>Canine osteosarcoma is an aggressive cancer, comprising 85% of canine bone neoplasms. Current treatment practices of surgery and chemotherapy increase 1-year survival by only 45%. The curcumin analogue RL71, has demonstrated potent in vitro and in vivo efficacy in several models of human breast cancer through increased apoptosis and cell cycle arrest. Thus, the present study aimed to investigate efficacy of curcumin analogues in two canine osteosarcoma cell lines. Osteosarcoma cell viability was assessed using the sulforhodamine B assay and mechanisms of action were determined by analysing the levels of cell cycle and apoptotic regulatory proteins via Western blotting. Further evidence was obtained using flow cytometry to detect cell cycle distribution and the number of apoptotic cells. RL71 was the most potent curcumin analogue with EC<sub>50</sub> values of 0.64 ± 0.04 and 0.38 ± 0.009 μM (n = 3) in D-17 (commercial) and Gracie canine osteosarcoma cells, respectively. RL71 significantly increased the ratio of cleaved-caspase 3 to pro-caspase 3 and the level of apoptotic cells at the 2× and 5× EC<sub>50</sub> concentration (p < 0.001, n = 3). Furthermore, at the same concentration, RL71 significantly increased the number of cells in the G2/M phase. In conclusion, RL71 has potent cytotoxic activity in canine osteosarcoma cells triggering G2/M arrest and apoptosis at concentrations achievable in vivo. Future research should further investigate molecular mechanisms for these changes in other canine osteosarcoma cell lines prior to in vivo investigation.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"595-604"},"PeriodicalIF":2.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9767545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel L Gustafson, Lindsey O Viola, Christina G Towers, Sunetra Das, Dawn L Duval, Kristen M Van Eaton
{"title":"Sensitivity of osteosarcoma cell lines to autophagy inhibition as determined by pharmacologic and genetic manipulation.","authors":"Daniel L Gustafson, Lindsey O Viola, Christina G Towers, Sunetra Das, Dawn L Duval, Kristen M Van Eaton","doi":"10.1111/vco.12937","DOIUrl":"10.1111/vco.12937","url":null,"abstract":"<p><p>Pharmacologic inhibition of autophagy can be achieved using lysosomotropic agents such as hydroxychloroquine (HCQ) that interfere with fusion of the autophagosome to the lysosome thus preventing completion of the recycling process. The goal of the present study is to determine the sensitivity of eight canine (cOSA) and four human (hOSA) osteosarcoma tumour cell lines to antiproliferative and cytotoxic effects of lysosomal autophagy inhibitors, and to compare these results to the autophagy-dependence measured using a CRISPR/Cas9 live-cell imaging assay in OSA and other tumour cell lines. Antiproliferative and cytotoxic response to HCQ and Lys05 was determined using live cell imaging and YOYO-1 staining. CRISPR/Cas9 live cell imaging screen was done using species specific guide RNA's and transfection of reagents into cells. Response to autophagy core genes was compared to response to an essential (PCNA) and non-essential (FOXO3A) gene. cOSA and hOSA cell lines showed similar antiproliferative and cytotoxic responses to HCQ and Lys05 with median lethal dose (D<sub>m</sub> ) values ranging from 4.6-15.8 μM and 2.1-5.1 μM for measures of anti-proliferative response, respectively. A relationship was observed between antiproliferative responses to HCQ and Lys05 and VPS34 CRISPR score with D<sub>m</sub> values correlating with VPS34 response (r = 0.968 and 0.887) in a species independent manner. The results show that a subset of cOSA and hOSA cell lines are autophagy-dependent and sensitive to HCQ at pharmacologically-relevant exposures.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"726-738"},"PeriodicalIF":2.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10302555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rebecca Stokes, Brandan G Wustefeld-Janssens, Whitney Hinson, Dominique J Wiener, Danielle Hollenbeck, Judith Bertran, Megan Mickelson, Carolyn L Chen, Laura Selmic, Ali Aly, Galina Hayes
{"title":"Surgical and oncologic outcomes in dogs with malignant peripheral nerve sheath tumours arising from the brachial or lumbosacral plexus.","authors":"Rebecca Stokes, Brandan G Wustefeld-Janssens, Whitney Hinson, Dominique J Wiener, Danielle Hollenbeck, Judith Bertran, Megan Mickelson, Carolyn L Chen, Laura Selmic, Ali Aly, Galina Hayes","doi":"10.1111/vco.12938","DOIUrl":"10.1111/vco.12938","url":null,"abstract":"<p><p>Malignant peripheral nerve sheath tumours (MPNST) of a plexus nerve or nerve root cause significant morbidity and present a treatment challenge. The surgical approach can be complex and information is lacking on outcomes. The objective of this study was to describe surgical complication rates and oncologic outcomes for canine MPNST of the brachial or lumbosacral plexus. Dogs treated for a naïve MPNST with amputation/hemipelvectomy with or without a laminectomy were retrospectively analysed. Oncologic outcomes were disease free interval (DFI), overall survival (OS), and 1- and 2-year survival rates. Thirty dogs were included. The surgery performed was amputation alone in 17 cases (57%), and amputation/hemipelvectomy with laminectomy in 13 cases (43%). Four dogs (13%) had an intraoperative complication, while 11 dogs (37%) had postoperative complications. Histologic margins were reported as R0 in 12 dogs (40%), R1 in 12 dogs (40%), and R2 in five dogs (17%). No association was found between histologic grade and margin nor extent of surgical approach and margin. Thirteen dogs (46%) had recurrence. The median DFI was 511 days (95% CI: 140-882 days). The median disease specific OST was 570 days (95% CI: 467-673 days) with 1- and 2-year survival rates of 82% and 22% respectively. No variables were significantly associated with recurrence, DFI, or disease specific OST. These data show surgical treatment of plexus MPNST was associated with a high intra- and postoperative complication rate but relatively good disease outcomes. This information can guide clinicians in surgical risk management and owner communication regarding realistic outcomes and complications.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"739-747"},"PeriodicalIF":2.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41116585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Timothy Estabrooks, Anastasia Gurinovich, Jodie Pietruska, Benjamin Lewis, Garrett Harvey, Gerald Post, Lindsay Lambert, Aubrey Miller, Lucas Rodrigues, Michelle E White, Christina Lopes, Cheryl A London, Kate Megquier
{"title":"Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma.","authors":"Timothy Estabrooks, Anastasia Gurinovich, Jodie Pietruska, Benjamin Lewis, Garrett Harvey, Gerald Post, Lindsay Lambert, Aubrey Miller, Lucas Rodrigues, Michelle E White, Christina Lopes, Cheryl A London, Kate Megquier","doi":"10.1111/vco.12925","DOIUrl":"10.1111/vco.12925","url":null,"abstract":"<p><p>Canine hemangiosarcoma (HSA) is an aggressive cancer of endothelial cells with short survival times. Understanding the genomic landscape of HSA may aid in developing therapeutic strategies for dogs and may also inform therapies for the rare and aggressive human cancer angiosarcoma. The objectives of this study were to build a framework for leveraging real-world genomic and clinical data that could provide the foundation for precision medicine in veterinary oncology, and to determine the relationships between genomic and clinical features in canine splenic HSA. One hundred and nine dogs with primary splenic HSA treated by splenectomy that had tumour sequencing via the FidoCure® Precision Medicine Platform targeted sequencing panel were enrolled. Patient signalment, weight, metastasis at diagnosis and overall survival time were retrospectively evaluated. The incidence of genomic alterations in individual genes and their relationship to patient variables including outcome were assessed. Somatic mutations in TP53 (n = 44), NRAS (n = 20) and PIK3CA (n = 19) were most common. Survival was associated with presence of metastases at diagnosis and germline variants in SETD2 and NOTCH1. Age at diagnosis was associated with somatic NRAS mutations and breed. TP53 and PIK3CA somatic mutations were found in larger dogs, while germline SETD2 variants were found in smaller dogs. We identified both somatic mutations and germline variants associated with clinical variables including age, breed and overall survival. These genetic changes may be useful prognostic factors and provide insight into the genomic landscape of hemangiosarcoma.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"623-633"},"PeriodicalIF":2.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41171709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}