Mammary tumor associated Hspb1 mutation and screening of eight cat populations of the world (original) (raw)
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Hspb1 and Tp53 Mutation and Expression Analysis in Cat Mammary Tumors
Iranian Journal of Biotechnology
Background The word "cancer" is so fearsome and attention seeking for victims, practitioners and guardians regardless the type of species afflicted. Mammary adenocarcinoma is the third most common cancer in the cats (1). Eighty percent of the total cases are malignant while 10-20% appeared as benign,sooner or later turn into malignant (2). Malignant tumors are equally lethal in animals as they are in humans and several animal cancers e.g. mammary adenocarcinoma in the cat are the best model for studying human cancer due to the resemblance in the cell morphology, histopathology, risk factors and prognosis (3, 4). Mammary tumor is a significant health concern in humans and small animals, so especial emphasis was given to ascertain cancer associated sequence number variant (SNVs) and gene expression profiling of Hspb1 and Tp53 genes in this neoplasm (5, 6). Molecular diagnostic biomarkers are getting much attention now in the field of oncology, but still there
International Journal of Molecular Sciences, 2012
The human ERBB2 proto-oncogene is widely considered a key gene involved in human breast cancer onset and progression. Among spontaneous tumors, mammary tumors are the most frequent cause of cancer death in cats and second most frequent in humans. In fact, naturally occurring tumors in domestic animals, more particularly cat mammary tumors, have been proposed as a good model for human breast cancer, but critical genetic and molecular information is still scarce. The aims of this study include the analysis of the
Medycyna Weterynaryjna, 2016
Association between GGA1 gene polymorphisms and occurrence of mammary mixed tumours and aging in domestic bitches Summary In recent years the number of malignant mammary gland tumor occurrences in domestic bitches has increased. This may be related to advanced diagnostic technologies, availability of a quick diagnosis, as well as genomic changes. Still the main genetic reasons for tumor development are frequently occurring gene mutations and/ or polymorphisms. The mutations in target genes often lead to amino acid changes in the structure of proteins, which may be the reason for uncontrolled cells proliferation, and induction and growth. Therefore, in this article we described the analysis of mutation/polymorphisms frequency of the GGA1 gene in association with canine malignant mammary gland tumor occurrence and aging. In this study, blood samples were obtained from 22 female dogs diagnosed with mammary tumors. Moreover, blood samples from geriatric (> 5 to 10 years old; n = 15), mature adult (> 2 to 5 years old; n = 10) and young (from 1 to 2 years old; n = 11) dogs were also collected. 36 bitches diagnosed on account of other reasons served as controls. After the Sanger sequencing analysis, 14 single nucleotide variations were identified, of which 3 were already known polymorphisms and 11 novel variations. We observed differences in frequencies for 4 polymorphisms (g.A-172T, c.T24C, c.A692G, c.C1185T) between cases and controls. Moreover, we found increased prevalence of heterozygotes and alternative alleles in 3 polymorphisms (g.A-172T, c.A692G, c.C1185T) in the tumor diagnosed group as compared to the control. Although the results were not statistically significant, it is worth mentioning the slightly different pattern of genetic segregation of alleles in the abovementioned polymorphisms in control and tumor patients.
Molecular based subtyping of feline mammary carcinomas and clinicopathological characterization
The Breast, 2016
Molecular classification of feline mammary carcinomas (FMC) from which specific behavioral patterns may be estimated has potential applications in veterinary clinical practice and in comparative oncology. In this perspective, the main goal of this study was to characterize both the clinical and the pathological features of the different molecular phenotypes found in a population of FMC (n ¼ 102), using the broadly accepted IHC-based classification established by St. Gallen International Expert Consensus panel. The luminal B/HER2-negative subtype was the most common (29.4%, 30/102) followed by luminal B/ HER2-positive subtype (19.6%, 20/102), triple negative basal-like (16.7%, 17/102), luminal A (14.7%, 15/ 102), triple negative normal-like (12.7%, 13/102) and finally, HER2-positive subtype (6.9%, 7/102). Luminal A subtype was significantly associated with smaller tumors (p ¼ 0.024) and with well differentiated ones (p < 0.001), contrasting with the triple negative basal-like subtype, that was associated with larger and poorly differentiated tumors (p < 0.001), and with the presence of necrotic areas in the tumoral lesion (p ¼ 0.003). In the survival analysis, cats with Luminal A subtype presented the highest survival time (mean OS ¼ 943.6 days) and animals with triple negative basal-like subtype exhibited the lowest survival time (OS mean ¼ 368.9 days). Moreover, two thirds (64%, 32/50) of the queens with multiple primary tumors showed different molecular subtypes in each carcinoma, revealing that all independent lesions should be analyzed in order to improve the clinical management of animals. Finally, the similarities between the subtypes of feline mammary tumors and human breast cancer, reveal that feline can be a valuable model for comparative studies.
Influence of Comt Genotypes on Prognosis of Canine Mammary Tumors
Veterinary Pathology - VET PATHOL, 2009
Catechol-O-methyltransferase (COMT) is an important enzyme involved in inactivation of catechol estrogens, which are metabolites with carcinogenic properties. Some investigations in human breast cancer associate a genetic polymorphism in the COMT gene (COMT val158met) with an increased risk and poor clinical progression of the disease. In dogs, there are 2 recognized single nucleotide polymorphisms in the COMT gene (COMTG216A and COMTG482A); however, their influence on the outcome of mammary neoplasms has never been investigated. The purpose of this study is to investigate the influence of COMT in the clinical progression of canine mammary tumors, namely in recurrence, metastasis and survival by testing 2 SNPs (G216A and G482A), and 2 genotypes of the COMT gene. A case series was conducted analyzing genomic DNA samples by polymerase chain reaction-restriction fragment length polymorphism from 80 bitches with mammary tumors. Animals were submitted to an active follow-up study for a period of 24 months after surgery. We observed that bitches carrying both genetic variations simultaneously are more likely to develop recurrence of mammary lesions. Our results demonstrate a possible role for COMT genotypes in the outcome of mammary neoplasms in the dog. Identifying a genetic factor predictive of recurrence may be useful in selecting the most effective surgical approach for canine mammary neoplasms.
Worldwide, canine mammary cancer (CMC) is the most frequent type of neoplasia in female dogs, and it is three times more frequent in dogs than in humans. In Colombia, CMC is the second most frequent type of cancer, after skin neoplasia. Genetics is one of the most important factors involved in any type of cancer, and the genetic basis of this disease is reflected through line breeding due to changes in allelic frequencies that are traceable using molecular markers. This study aimed to detect single nucleotide polymorphisms (SNPs) associated with CMC in blood samples collected from collected from healthy and CMC female dogs at
Canine mammary tumor risk is associated with polymorphisms in RAD51 and STK11 genes
Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc, 2018
Cancer is a complex disease involving genetic and phenotypic changes. Several single nucleotide polymorphisms (SNPs) have been associated with the risk of breast cancer development in women; however, little is known regarding their influence on canine mammary tumor risk. We assessed the influence of SNPs in genes related to human breast cancer susceptibility, with respect to the risk of development of mammary tumors in dogs. Sixty-seven canine SNPs in proto-oncogenes, tumor suppressor genes, genes involved in DNA repair, and in hormonal metabolism were evaluated in 212 bitches with mammary tumors and in 161 bitches free of mammary neoplasia. A significant association with mammary neoplasia risk was identified for 2 SNPs in RAD51 ( rs23623251 and rs23642734) and one SNP in the STK11 gene ( rs22928814). None of the other SNPs were related to the risk of mammary tumor development. The identification of genetic profiles associated with risk of mammary neoplasia is of great importance, s...
Original Article: Feline Mammary Carcinomas as a Model for Human Breast Cancer: A Case-series Study
2023
Introduction: Feline mammary carcinoma (FMC) is the third most common cancer in cats. Diagnosis of mammary gland tumors (MGTs) increases every year; this might be due to the rise in occurrence or improvements in methods of detecting MGTs. Determinants associated withtheir occurrence are studied in the present paper. Materials and Methods: In this case-series study, 40 queens with FMC were referred to the determined major veterinary hospitals of Tehran for treatment between 2020 and 2022; their mammary carcinoma had been confirmed by the attended pathologist. Different parameters including age of cancer diagnosis, breed, reproductive status, BCS, diet type, parity, tumor size, multiple tumors, ER and PR status, location and type of treatment were recorded on the day of presentation using a checklist. Results: Domestic short hairs were overrepresented. Also, queens with old age (more than 9 years old), homemade diet, sexually intact status, no parity, obesity, ER and PR positivity had higher frequency towards developing FMC. Imbalanced homemade diet energy is a speculated cause. Conclusion: Humans and their companion animals share the same environment, thus being exposed to the same environmental risks. Although canine mammary tumors have been the focus of human breast cancer (HBC) modeling, this study also aimed to compare current feline mammary carcinoma determinants with previously defined human breast cancer determinants to produce a model. Based on the results of this study, we concluded that FMCs are a proper model to study HBC.
Molecular Biological Aspects on Canine and Human Mammary Tumors
Veterinary Pathology, 2010
The high incidence of mammary tumor disease reported in certain canine breeds suggests a significant genetic component, as has already been described in human familial breast cancer—in BRCA1- and BRCA2-associated breast cancer in particular. The identification of genetic risk factors is critical to improvements in the prevention, diagnosis, and treatment of these tumors. In recent years, there has been significant progress in developing the tools and reagents necessary to analyze the canine genome. This work has culminated in a high-quality draft genome sequence, as well as a single-nucleotide polymorphism map and single-nucleotide polymorphism arrays for genomewide association analysis. These tools provide an unprecedented opportunity to characterize the genetic influences in canine diseases such as cancer, eventually allowing for exploration of more effective therapies. Given the high homology between the canine genome sequence and its human counterpart—as well as the many similar...
Molecular Phenotype of Primary Mammary Tumours and Distant Metastases in Female Dogs and Cats
Journal of Comparative Pathology, 2013
Distant metastases represent a major step in the progression and fatal outcome of canine and feline mammary carcinomas. Recent studies have characterized the molecular phenotypes of mammary tumours and provided information on molecules that may allow targeted therapy in sites from which the tumours may not readily be surgically resected. Molecular phenotypes were determined immunohistochemically in three feline and two canine cases of mammary neoplasia, each presenting with multiple distant metastases. These tumours and their metastases often overexpressed the c-erbB-2 phenotype. A basal-like phenotype was found in the distant metastases from two cases. These findings suggest that canine and feline mammary tumours with distant metastases may be amenable to novel targeted therapies.