研究者データベース
| 石崎 禎太(イシザキ テイタ) |
| 獣医学研究院 附属動物病院 |
| 准教授 |
Last Updated :2023/12/05
研究活動情報
論文
- Yu Asari, Jumpei Yamazaki, Oo Thandar, Tamami Suzuki, Keisuke Aoshima, Kyosuke Takeuchi, Ryohei Kinoshita, Sangho Kim, Kenji Hosoya, Teita Ishizaki, Yumiko Kagawa, Jaroslav Jelinek, Shoko Yokoyama, Noboru Sasaki, Hiroshi Ohta, Kensuke Nakamura, Mitsuyoshi TakiguchiVeterinary medicine and science 2023年07月22日BACKGROUND: Canine hepatocellular tumours (HCTs) are common primary liver tumours. However, the exact mechanisms of tumourigenesis remain unclear. Although some genetic mutations have been reported, DNA methylation alterations in canine HCT have not been well studied. OBJECTIVES: In this study, we aimed to analyse the DNA methylation status of canine HCT. METHODS: Tissues from 33 hepatocellular carcinomas, 3 hepatocellular adenomas, 1 nodular hyperplasia, 21 non-tumour livers from the patients and normal livers from 5 healthy dogs were used. We analysed the DNA methylation levels of 72,367 cytosine-guanine dinucleotides (CpG sites) in all 63 samples. RESULTS AND CONCLUSIONS: Although a large fraction of CpG sites that were highly methylated in the normal liver became hypomethylated in tumours from most patients, we also found some patients with less remarkable change or no change in DNA methylation. Hierarchical clustering analysis revealed that 32 of 37 tumour samples differed from normal livers, although the remaining 5 tumour livers fell into the same cluster as normal livers. In addition, the number of hypermethylated genes in tumour livers varied among tumour cases, suggesting various DNA methylation patterns in different tumour groups. However, patient and clinical parameters, such as age, were not associated with DNA methylation status. In conclusion, we found that HCTs undergo aberrant and diverse patterns of genome-wide DNA methylation compared with normal liver tissue, suggesting a complex epigenetic mechanism in canine HCT.
- Jumpei Yamazaki, Yuki Matsumoto, Jaroslav Jelinek, Teita Ishizaki, Shingo Maeda, Kei Watanabe, Genki Ishihara, Junya Yamagishi, Mitsuyoshi TakiguchiScientific reports 11 1 10005 - 10005 2021年05月11日DNA methylation plays important functions in gene expression regulation that is involved in individual development and various diseases. DNA methylation has been well studied in human and model organisms, but only limited data exist in companion animals like dog. Using methylation-sensitive restriction enzyme-based next generation sequencing (Canine DREAM), we obtained canine DNA methylation maps of 16 somatic tissues from two dogs. In total, we evaluated 130,861 CpG sites. The majority of CpG sites were either highly methylated (> 70%, 52.5-64.6% of all CpG sites analyzed) or unmethylated (< 30%, 22.5-28.0% of all CpG sites analyzed) which are methylation patterns similar to other species. The overall methylation status of CpG sites across the 32 methylomes were remarkably similar. However, the tissue types were clearly defined by principle component analysis and hierarchical clustering analysis with DNA methylome. We found 6416 CpG sites located closely at promoter region of genes and inverse correlation between DNA methylation and gene expression of these genes. Our study provides basic dataset for DNA methylation profiles in dogs.
- T Ishizaki, J Yamazaki, J Jelinek, K Aoshima, T KimuraResearch in veterinary science 132 521 - 526 2020年10月Canine malignant melanoma is a common cancer with a high mortality rate. Although previous studies have evaluated various aspects of this tumour, the exact mechanism of tumourigenesis remains unknown. Epigenetic mechanisms, such as DNA methylation, have recently gained attention as aetiological factors for neoplasia in humans. This study aimed to analyse genome-wide DNA methylation patterns in canine malignant melanoma based on next-generation sequencing data. A total of 76,213 CpG sites, including 29,482 sites in CpG islands (CGIs), were analysed using next-generation sequencing of methylation-specific signatures, obtained by sequential digestion with enzymes, to compare normal oral mucosal samples from four healthy dogs, four canine melanoma cell lines (3 oral cavity and 1 skin), and five clinical samples of oral canine melanoma. Malignant melanoma showed increased methylation at thousands of normally unmethylated CpG sites in CGIs and decreased methylation at normally methylated CpG sites in non-CGIs. Interestingly, the promoter regions of 81-393 genes were hypermethylated; 23 of these genes were present in all melanoma cell lines and melanoma clinical samples. Among these 23 genes, six genes with "sequence-specific DNA binding" annotation were significantly enriched, including three Homeobox genes-HMX2, TLX2, and HOXA9-that may be involved in the tumourigenesis of canine malignant melanoma. This study revealed widespread alterations in DNA methylation and a large number of hypermethylated genes in canine malignant melanoma.
- Hiroshi Ohta, Jumpei Yamazaki, Jaroslav Jelinek, Teita Ishizaki, Yumiko Kagawa, Nozomu Yokoyama, Noriyuki Nagata, Noboru Sasaki, Mitsuyoshi TakiguchiThe Journal of veterinary medical science 82 5 632 - 638 2020年03月25日 [査読有り][通常論文]
DNA methylation is the covalent modification of methyl groups to DNA mostly at CpG dinucleotides and one of the most studied epigenetic mechanisms that leads to gene expression variability without affecting the DNA sequence. Genome-wide analysis of DNA methylation identified the signatures that could define subtypes of human lymphoma patients. The objective of this study was to conduct the genome-wide analysis of DNA methylation in dogs with gastrointestinal lymphoma (GIL). Genomic DNA was extracted from endoscopic biopsies from 10 dogs with GIL. We performed Digital Restriction Enzyme Assay of DNA Methylation (DREAM) for genome-wide DNA methylation analysis that could provide highly quantitative information on DNA methylation levels of CpG sites across the dog genome. We successfully obtained data of quantitative DNA methylation level for 148,601-162,364 CpG sites per GIL sample. Next, we analyzed 83,132 CpG sites to dissect the differences in DNA methylation between GIL and normal peripheral blood mononuclear cells (PBMCs). We found 383-3,054 CpG sites that were hypermethylated in GIL cases compared to PBMCs. Interestingly, 773 CpG sites including promoter regions of 61 genes were identified to be commonly hypermethylated in more than half of the cases, suggesting conserved DNA methylation patterns that are abnormal in GIL. This study revealed that there was a large number of hypermethylated sites that are common in most of canine GIL. These abnormal DNA methylation could be involved in tumorigenesis of the canine GIL. - Teita Ishizaki, Jumpei Yamazaki, Shinji Meagawa, Nozomu Yokoyama, Keisuke Aoshima, Mitsuyoshi Takiguchi, Takashi KimuraVeterinary and comparative oncology 2020年03月18日 [査読有り][通常論文]
Canine malignant melanoma is a common cancer with a high mortality rate and is a clinically important disease. DNA methylation has been considered to be a potential tumorigenic mechanism through aberrant DNA methylation at promoter region which represses gene transcription. Global hypomethylation could also facilitate chromosome instability. There are few reports regarding DNA methylation in canine malignant melanoma; therefore, the purpose of this study was to examine DNA methylation status of long interspersed nucleotide element-1 (LINE-1) to be a surrogate marker of genome-wide methylation changes in this disease. We measured levels of DNA methylation of two adjacent cytosine-guanine sites on CpG island (CGI) at the putative promoter of canine LINE-1 sequence by bisulphite-pyrosequencing in 41 canine melanoma patient samples as well as six cell lines compared with normal mucosae. The survival rates were obtained from owners or medical records. We found DNA methylation levels of LINE-1 in normal mucosae were methylated. Interestingly, both melanoma cell lines and clinical melanoma samples showed remarkable hypomethylation. In addition, patients with lower LINE-1 methylation showed worse prognosis than those with higher LINE-1 methylation, though the difference did not reach statistical significance (P = .09). Here, we demonstrate that hypomethylation of LINE-1 is an epigenetically aberrant feature in canine melanoma with possible prognostic value.
書籍
- Veterinary Oncology石崎 禎太 (範囲:脾臓の細胞診)
インターズー 2015年04月 - CAP (Companion Animal Practice)石崎 禎太 (範囲:病理学的にみた鼻腔内腫瘍)
緑書房 2013年09月
講演・口頭発表等
- 教育講演 細胞診断学第15回 日本獣医がん学会 2016年06月
- 米国獣医臨床病理学専門医への道 [通常講演]石崎 禎太日本獣医臨床病理学会 2015年学術大会 2015年05月
- これくらいは知っておきたい腎泌尿器検査の解釈 [通常講演]石崎 禎太第11回 鹿児島大学小動物臨床フォーラム 2015年03月
- 胸水・腹水の細胞診 [通常講演]石崎 禎太日本獣医臨床病理学会 2014年学術大会 2014年05月