| Theme | Molecular biology of colorectal tumors | |
|---|---|---|
| Title | Aberrant epigenomic alterations in colorectal neoplasm | |
| Publish Date | 2018/09 | |
| Author | Atsushi Kaneda | Department of Molecular Oncology, Graduate School of Medicine, Chiba University |
| Author | Koichi Yagi | Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo |
| Author | Eiji Sakai | Department of Molecular Oncology, Graduate School of Medicine, Chiba University / Department of Gastroenterology, Kanto Medical Center, NTT East |
| Author | Keisuke Matsusaka | Department of Molecular Oncology, Graduate School of Medicine, Chiba University |
| Author | Kiyoko Takane | Department of Molecular Oncology, Graduate School of Medicine, Chiba University / Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo |
| Author | Atsushi Okabe | Department of Molecular Oncology, Graduate School of Medicine, Chiba University |
| [ Summary ] | Epigenome is the information concerning modification of the genome, e.g. DNA methylation or histone methylation or acetylation, which plays critical roles in regulation of gene expression and determination of cellular states. Aberrant DNA methylation is known as one of the major mechanisms which inactivate tumor suppressor genes. Comprehensive analyses of DNA methylation have stratified colorectal cancer into several subgroups in relation to specific DNA methylation accumulation patterns. Accumulation of high levels of methylation in combination with BRAF mutations are characteristic of the serrated pathways, but not of the adenoma-carcinoma sequence through which conventional adenomas develop. In de novo pathways, laterally spreading tumors generate intermediate- and low methylation epigenotypes, accompanied by different genetic features and different macroscopic morphologies. These methylation accumulations, with specific genomic aberrations, are primarily completed by the adenoma stage. Additional molecular aberrations, such as TP53 mutations, are suspected of leading to cancer development with the corresponding epigenotype. Accumulation of DNA methylation, possibly accelerated by ageing and inflammation or inhibited by other environmental factors, or other epigenomic aberrations e.g. loss of imprinting, are thought to occur during the early stages of carcinogenesis, and play causal roles in colorectal carcinogenesis. | |