My research during this current visit was an extension of the cooperative research initiated in 1996 with Dr Takao Sekiya and Dr Masahiko Shiraishi of the Oncogene Division at the National Cancer Center Research Institute. In the current research project we turned our attention to the analysis of methylation of CpG islands as a possible means of epigenetic gene silencing in cancer. Epigenetic gene silencing is associated with many biological phenomena such as X chromosome inactivation and genomic imprinting. In each of these cases one of the alleles is trancriptionally inactive without any apparent alteration of nucleotide sequences. Although the mechanism of epigenetic silencing is far from clear, accumulating evidence strongly suggests that DNA methylation is closely associated with long-term repression of transcription.
Cancer develops following the accumulation of genetic and epigenetic changes.
Genetic perturbations, in which changes in the specific nucleotide sequence of a gene occur, have been extensively investigated. However, epigenetic changes remain less well understood. In cancer, methylation of CpG islands is considered to be one of the major epigenetic aberrations that cause gene inactivation, although as yet little is known of the genes affected by CpG island methylation. To address this important issue, cooperative research between Dr Masahiko Shiraishi, Dr Takao Sekiya and their laboratory group and myself has been established. The starting point for the current collaboration was to follow the creation of a library containing methylated CpG island fragments.