Animal Models, Genetic and Genomic Studies in Cancer and Its Therapy

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: 15 September 2025 | Viewed by 5837

Special Issue Editors

Molecular and Cellular Biology, Department of Molecular and Cellular Biology, Kennesaw State University, Statesboro, GA, USA
Interests: cancer biology; human genetics; cell and molecular biology; drosophila
Special Issues, Collections and Topics in MDPI journals
Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL, USA
Interests: ovarian cancer; cancer stem cell; epigenetics; metabolism; ROS; chemo resistance
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Graduate School of Medicine, Kyoto University, Kyoto, Japan
Interests: cancer cell evolution; polyploidy; tissue homeostasis; morphogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer is essentially a genetic disease. Accumulated genetic mutations accelerate genome instability, which eventually leads to the uncontrollable growth of the tumor. Many cancer types have poor prognosis due to their clinical heterogeneity and molecular diversity. There is a great need to understand cancer biology and to create animal models to advance scientific knowledge and facilitate cancer treatments.

This Special Issue of Genes aims to highlight the most recent advances in animal modeling and its application in the field of cancer research. We invite authors to submit reviews, original articles, new experimental and computational methods, and commentaries that focus on any of the following topics: different animal models of cancer, applications of animal modeling, and translational research using animals in cancer research and the clinical field. We look forward to your contributions.

Dr. Dongyu Jia
Dr. Yinu Wang
Dr. Yoichiro Tamori
Guest Editors

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Keywords

  • animal model
  • cancer model
  • application
  • translational research
  • cancer biology

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Published Papers (3 papers)

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Research

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15 pages, 732 KiB  
Article
Expression Profile of Twelve Transcripts as a Supporting Tool for the Molecular Characterization of Canine Cutaneous Mast Cell Tumors at Diagnosis: Association with Histological Grading and Clinical Staging
by Mery Giantin, Ludovica Montanucci, Rosa Maria Lopparelli, Roberta Tolosi, Alfredo Dentini, Valeria Grieco, Damiano Stefanello, Silvia Sabattini, Laura Marconato, Marianna Pauletto and Mauro Dacasto
Genes 2025, 16(3), 340; https://doi.org/10.3390/genes16030340 - 14 Mar 2025
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Abstract
Background/Objectives: Mast cell tumors (MCTs) are the second most common malignant neoplasms in dogs. Histopathological grading and clinical staging are the main tools for estimating biological behavior and disease extent; thus, both are essential for therapeutic decision-making and prognostication. However, the biological behavior [...] Read more.
Background/Objectives: Mast cell tumors (MCTs) are the second most common malignant neoplasms in dogs. Histopathological grading and clinical staging are the main tools for estimating biological behavior and disease extent; thus, both are essential for therapeutic decision-making and prognostication. However, the biological behavior of MCTs in dogs is variable, and it sometimes deviates from expectations. In a previous study, we identified 12 transcripts whose expression profile allowed a clear distinction between Kiupel low-grade and high-grade cutaneous MCTs (cMCTs) and was associated with prognosis. Building on these findings, this study evaluated the predictive potential of these transcripts’ expression profiles in classifying cMCTs into low-grade and high-grade. Methods: A logistic regression classifier based on the expression profiles of the identified transcripts and able to classify cMCTs as low- or high-grade was developed and subsequently tested on a novel dataset of 50 cMCTs whose expression profiles have been determined in this study through qPCR. Results: The developed logistic regression classifier reaches an accuracy of 67% and an area under the receiver operating characteristic curve (AUC) of 0.76. Interestingly, the molecular classification clearly identifies stage-IV disease (90% true positive rate). Conclusions: qPCR analysis of these biomarkers combined with the machine learning-based classifier might serve as a tool to support cMCT clinical management at diagnosis. Full article
(This article belongs to the Special Issue Animal Models, Genetic and Genomic Studies in Cancer and Its Therapy)
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13 pages, 1561 KiB  
Article
Canine Histiocytic and Hemophagocytic Histiocytic Sarcomas Display KRAS and Extensive PTPN11/SHP2 Mutations and Respond In Vitro to MEK Inhibition by Cobimetinib
by Ya-Ting Yang, Alexander I. Engleberg, Ishana Kapoor, Keita Kitagawa, Sara A. Hilburger, Tuddow Thaiwong-Nebelung and Vilma Yuzbasiyan-Gurkan
Genes 2024, 15(8), 1050; https://doi.org/10.3390/genes15081050 - 9 Aug 2024
Cited by 1 | Viewed by 1719
Abstract
Histiocytic sarcoma (HS) is a rare and highly aggressive cancer in humans and dogs. In dogs, it has a high prevalence in certain breeds, such as Bernese mountain dogs (BMDs) and flat-coated retrievers. Hemophagocytic histiocytic sarcoma (HHS) is a unique form of HS [...] Read more.
Histiocytic sarcoma (HS) is a rare and highly aggressive cancer in humans and dogs. In dogs, it has a high prevalence in certain breeds, such as Bernese mountain dogs (BMDs) and flat-coated retrievers. Hemophagocytic histiocytic sarcoma (HHS) is a unique form of HS that presents with erythrophagocytosis. Due to its rareness, the study of HHS is very limited, and mutations in canine HHS patients have not been studied to date. In previous work, our research group identified two major PTPN11/SHP2 driver mutations, E76K and G503V, in HS in dogs. Here, we report additional mutations located in exon 3 of PTPN11/SHP2 in both HS and HHS cases, further supporting that this area is a mutational hotspot in dogs and that mutations in tumors and liquid biopsies should be evaluated utilizing comprehensive methods such as Sanger and NextGen sequencing. The overall prevalence of PTPN11/SHP2 mutations was 55.8% in HS and 46.2% in HHS. In addition, we identified mutations in KRAS, in about 3% of HS and 4% of HHS cases. These findings point to the shared molecular pathology of activation of the MAPK pathway in HS and HHS cases. We evaluated the efficacy of the highly specific MEK inhibitor, cobimetinib, in canine HS and HHS cell lines. We found that the IC50 values ranged from 74 to 372 nM, which are within the achievable and tolerable ranges for cobimetinib. This finding positions cobimetinib as a promising potential candidate for future canine clinical trials and enhances our understanding of the molecular defects in these challenging cancers. Full article
(This article belongs to the Special Issue Animal Models, Genetic and Genomic Studies in Cancer and Its Therapy)
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Review

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30 pages, 1918 KiB  
Review
Cell-Free DNA Hydroxymethylation in Cancer: Current and Emerging Detection Methods and Clinical Applications
by Janice J. N. Li, Geoffrey Liu and Benjamin H. Lok
Genes 2024, 15(9), 1160; https://doi.org/10.3390/genes15091160 - 3 Sep 2024
Viewed by 3029
Abstract
In the era of precision oncology, identifying abnormal genetic and epigenetic alterations has transformed the way cancer is diagnosed, managed, and treated. 5-hydroxymethylcytosine (5hmC) is an emerging epigenetic modification formed through the oxidation of 5-methylcytosine (5mC) by ten-eleven translocase (TET) enzymes. DNA hydroxymethylation [...] Read more.
In the era of precision oncology, identifying abnormal genetic and epigenetic alterations has transformed the way cancer is diagnosed, managed, and treated. 5-hydroxymethylcytosine (5hmC) is an emerging epigenetic modification formed through the oxidation of 5-methylcytosine (5mC) by ten-eleven translocase (TET) enzymes. DNA hydroxymethylation exhibits tissue- and cancer-specific patterns and is essential in DNA demethylation and gene regulation. Recent advancements in 5hmC detection methods and the discovery of 5hmC in cell-free DNA (cfDNA) have highlighted the potential for cell-free 5hmC as a cancer biomarker. This review explores the current and emerging techniques and applications of DNA hydroxymethylation in cancer, particularly in the context of cfDNA. Full article
(This article belongs to the Special Issue Animal Models, Genetic and Genomic Studies in Cancer and Its Therapy)
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