Overexpression and Mutation of p53 Exons 4–8 in Canine Intestinal Adenocarcinoma

Cho, S.H.; Seung, Byung-Joon; Kim, S.-H.; Lim, Hyungjun; Sur, Jung Hyang

doi:10.1016/j.jcpa.2019.12.008

Cited by 10 publications

(12 citation statements)

References 15 publications

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“…Finally, it is worth highlighting the findings regarding the basal expression of the TP53 gene in plasma of dogs with mammary tumors. In both human and animal patients, TP53 overexpression, primarily assessed by IHC techniques in tumor tissues, is linked to poor prognosis and tumor progression confirming the usefulness of this oncogene as a tumor biomarker (43)(44)(45)(46). In our study, a differential expression of the TP53-wt gene has been observed in plasma and in tumor tissue in dogs.…”

Section: Discussionmentioning

confidence: 87%

Analysis of cell-free DNA concentration, fragmentation patterns and TP53 gene expression in mammary tumor-bearing dogs: A pilot study

et al. 2023

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IntroductionLiquid biopsy based on the analysis of circulating cell-free DNA (cfDNA), as well as on detection of point mutations by digital droplet PCR (ddPCR), has revolutionized the research in oncology. In recent years, this technique has been pioneering in veterinary medicine since it is a minimally invasive approach with very promising results for characterization of tumors.MethodsThe aim of this study was, firstly, to analyze the concentration and the fragmentation pattern of cfDNA of dogs with mammary tumors (n = 36) and healthy dogs (n = 5) and its correlation with clinicopathological data. Secondly, analysis of TP53 gene expression and the point mutation in the codon 245 were performed in cfDNA and in tumor tissues to assess their potential as plasma biomarkers.Results and discussionOur results highlighted that those dogs with worse clinicopathological characteristics (simple or undifferentiated carcinomas, higher histological grade and presence of peritumoral inflammation) shown higher cfDNA concentration and higher concentrations of short-fragments (<190 bp) than healthy dogs. In addition, although no detection of the point mutation in codon 245 of TP53 gene could be detected neither in plasma nor tumor tissue, an increased TP53 expression was detected in animals with tumors bearing malignant characteristics. Finally, a high concordance with TP53 gene expression in plasma and tumor tissue and cfDNA concentration was also found. The results derived from this work confirm the valuable potential of cfDNA and its fragments, as well as the analysis of TP53 expression in plasma as useful liquid biomarkers for clinical application in veterinary oncology.

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Section: Discussionmentioning

confidence: 87%

Analysis of cell-free DNA concentration, fragmentation patterns and TP53 gene expression in mammary tumor-bearing dogs: A pilot study

et al. 2023

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“…Strong immuno‐expression of p53 could represent accumulation of non‐functional but stable mutant protein, whereas absence of detectable expression could be considered incorrectly as the normal, vanishingly low levels of wildtype tp53, when actually p53 expression is truly absent because of missense mutations 44 . Despite this caveat, the results obtained by immunohistochemistry to detect tp53 mutations discussed in the following studies, 44,60,110 correlate with results obtained by PCR 108,111 and sequencing analysis 112 . All come to the same conclusion: p53 mutation can be used as a prognostic factor that its related to proliferation and malignancy of tumours.…”

Section: Selected Ddr Proteins and Their Potential Role In Canine Res...mentioning

confidence: 92%

“…Again, in this study, a validated antibody was used to detect p53, and we can add that we have tested the same antibody and observed p53 expression by western blot in canine cell extracts (BHS and AP, unpublished results). Furthermore, sequencing analysis revealed that 3 of the malignant tissues analysed carried a tp53 mutation 108 …”

Section: Selected Ddr Proteins and Their Potential Role In Canine Res...mentioning

confidence: 99%

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DNA damage response proteins in canine cancer as potential research targets in comparative oncology

Hernandez-Suarez

Gillespie

Pawlak

2022

Vet Comparative Oncology

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The DNA damage response (DDR) is a complex signal transduction network that is activated when endogenous or exogenous genotoxins damage or interfere with the replication of genomic DNA. Under such conditions, the DDR promotes DNA repair and ensures accurate replication and division of the genome. High levels of genomic instability are frequently observed in cancers and can stem from germline loss‐of‐function mutations in certain DDR genes, such as BRCA1, BRCA2, and p53, that form the basis of human cancer predisposition syndromes. In addition, mutation and/or aberrant expression of multiple DDR genes are frequently observed in sporadic human cancers. As a result, the DDR is considered to represent a viable target for cancer therapy in humans and a variety of strategies are under investigation. Cancer is also a significant cause of mortality in dogs, a species that offers certain advantages for experimental oncology. Domestic dogs present numerous inbred lines, many of which display predisposition to specific forms of cancer and the study of which may provide insight into the biological basis of this susceptibility. In addition, clinical trials are possible in dogs and may lead to therapeutic insights that could ultimately be extended to humans. Here we review what is known specifically about the DDR in dogs and discuss how this knowledge could be extended and exploited to advance experimental oncology in this species.

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“…We selected 21 documented canine intestinal tissues including additional samples remaining after the completion of a previous study, 5 from the histopathological database of the Department of Veterinary Pathology, Konkuk University, Seoul, South Korea, between 2005 and 2020. Nonneoplastic intestinal regions of samples 2, 5, 9, and 10 were included as nonneoplastic canine intestinal tissues.…”

Section: Methodsmentioning

confidence: 99%

EGFR Overexpression and Sequence Analysis of KRAS, BRAF, and EGFR Mutation Hot Spots in Canine Intestinal Adenocarcinoma

et al. 2021

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Epidermal growth factor receptor (EGFR) is overexpressed in many human colorectal cancers and anti-EGFR agents are employed as immunotherapies. However, KRAS, EGFR, and BRAF gene mutations can influence the activity of the anti-EGFR agents. We evaluated EGFR expression at protein and mRNA levels in canine intestinal adenocarcinomas using immunohistochemistry (IHC) and RNA in situ hybridization (RNA-ISH). We also investigated the mutation status of EGFR, KRAS, and BRAF to aid the development of anti-EGFR agents for canine intestinal adenocarcinoma. EGFR expression was highest in adenocarcinoma, followed by intramucosal neoplasia (adenoma and in situ carcinoma), and nonneoplastic canine intestinal tissue, at both protein ( P = .000) and mRNA ( P = .005) levels. The EGFR, KRAS, and BRAF genes showed wild-type sequences at the mutation hot spots in all 13 specimens. Thus, EGFR might serve as a promising diagnostic marker in canine intestinal adenocarcinoma, and further studies would be needed to develop EGFR-targeted anticancer therapies.

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Overexpression and Mutation of p53 Exons 4–8 in Canine Intestinal Adenocarcinoma

Cited by 10 publications

References 15 publications

Analysis of cell-free DNA concentration, fragmentation patterns and TP53 gene expression in mammary tumor-bearing dogs: A pilot study

Analysis of cell-free DNA concentration, fragmentation patterns and TP53 gene expression in mammary tumor-bearing dogs: A pilot study

DNA damage response proteins in canine cancer as potential research targets in comparative oncology

EGFR Overexpression and Sequence Analysis of KRAS, BRAF, and EGFR Mutation Hot Spots in Canine Intestinal Adenocarcinoma

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