Dataset Information

Heteroplasmic Mutations and Polymorphisms in the Cyb Gene of Mitochondrial DNA in Canine Mast Cell Tumours.

ABSTRACT: AIM:Identification of mutations and polymorphisms in the cytochrome b gene (Cyb) of mitochondrial DNA (mtDNA) in canine mast cell tumours and determinatiion of their association with the process of neoplastic transformation. MATERIALS AND METHODS:The samples comprised tumour tissues and blood obtained from 34 dogs of various breeds. Mutations and polymorphisms in the Cyb gene were detected using amplification and sequencing methods. RESULTS:Heteroplasmic mutations were detected at seven positions of mtDNA in 86% of the individuals. Blood and tumour heteroplasmy were recorded at five nucleotide positions of the Cyb gene, whereas tumour heteroplasmy was detected at two positions. Polymorphisms were detected at 14 Cyb gene positions in in the blood of 91% of dogs with mast cell tumours. CONCLUSION:The presence of numerous mutations and polymorphisms of Cyb in the blood and tumour tissues and the high frequency of heteroplasmy indicate their involvement in the process of neoplastic transformation in dogs.

SUBMITTER: Smiech A

PROVIDER: S-EPMC6364090 | biostudies-literature | 2019 Jan-Feb

REPOSITORIES: biostudies-literature

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Publications

Heteroplasmic Mutations and Polymorphisms in the <i>Cyb</i> Gene of Mitochondrial DNA in Canine Mast Cell Tumours.

Śmiech Anna A Ślaska Brygida B Bownik Adam A Grzybowska-Szatkowska Ludmiła L Dudka Jarosław J Łopuszyński Wojciech W

In vivo (Athens, Greece) 20190101 1

<h4>Aim</h4>Identification of mutations and polymorphisms in the cytochrome b gene (Cyb) of mitochondrial DNA (mtDNA) in canine mast cell tumours and determinatiion of their association with the process of neoplastic transformation.<h4>Materials and methods</h4>The samples comprised tumour tissues and blood obtained from 34 dogs of various breeds. Mutations and polymorphisms in the Cyb gene were detected using amplification and sequencing methods.<h4>Results</h4>Heteroplasmic mutations were dete ...[more]

PMID: 30587603

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Project description:Mast cell tumours (MCTs) are common neoplasms in dogs and are usually regarded as potentially malignant. Several studies have attempted to identify biomarkers to better predict biological behaviours for this tumour. The aim of this study was to identify pathways connected to clinical and histopathological malignancies, shorter survival times, and poor prognoses associated with MCTs. We performed genome-wide gene expression analyses on tissues obtained from 15 dogs with single MCTs, and identified two distinct tumour subtypes-high-risk and low-risk-associated with differences in histological grades, survival times, Ki67 indices, and occurrence of death due the disease. Comparative analyses of RNA sequence profiles revealed 71 genes that were differentially expressed between high- and low-risk MCTs. In addition to these analyses, we also examined gene co-expression networks to explore the biological functions of the identified genes. The network construction revealed 63 gene modules, of which 4 were significantly associated with the more aggressive tumour group. Two of the gene modules positively correlated with high-risk MCTs were also associated with cell proliferation and extracellular matrix-related terms. At the top of the extracellular matrix module category, genes with functions directly related to those of cancer-associated fibroblasts (CAFs) were identified. Immunohistochemical analyses also revealed a greater number of CAFs in high-risk MCTs. This study provides a method for the molecular characterisation of canine MCTs into two distinct subtypes. Our data indicate that proliferation pathways are significantly involved in malignant tumour behaviours, which are known to be relevant for the induction and maintenance of MCTs. Finally, animals presenting high-risk MCTs overexpress genes associated with the extracellular matrix that can be robustly linked to CAF functions. We suggest that CAFs in the MCT stroma contribute to cancer progression.

Dataset Information

Heteroplasmic Mutations and Polymorphisms in the Cyb Gene of Mitochondrial DNA in Canine Mast Cell Tumours.

Publications

Heteroplasmic Mutations and Polymorphisms in the <i>Cyb</i> Gene of Mitochondrial DNA in Canine Mast Cell Tumours.

Similar Datasets

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