Research Summary

Analysis of the occurrence and progression mechanism of cancer based on transcriptional and translational regulation mechanism

Abnormal transcription and translation in cancer cells make characteristic phenotypes which are different from normal cells. The details of RNA expression mechanism related to carcinogenesis is still not clearly understood.  We have comprehensively collected RNA information on both normal and cancer cells and constructed a database DBTSS / DBKERO that have accurate transcription start sites, RNA structures, and histone modifications. Also, we have reported that a part of the gene group called non-coding RNAs may encode a short peptide, same as mRNAs, and play a biologically significant role such as muscle regeneration. We are combining these data with public databases to make a catalog of RNA behavior for normal and cancer cells. We are also trying to understand cancer from the aspect of transcription and translation control by a bioinformatic approach such as artificial intelligence (AI) techniques.

Integration of environmental carcinogenesis and cancer genomics

An outbreak of cholangiocarcinoma among workers in a printing company in Osaka, Japan, was recently reported, and this disease was newly classified as an occupational disease by the Ministry of Health, Labour and Welfare of Japan in 2013. All of the patients had been exposed to high concentrations of chemical compounds, including 1,2-dichloropropane (1,2-DCP) and/or dichloromethane (DCM). We performed a genome-wide mutation analysis of four cases of occupational cholangiocarcinoma using genomic DNA samples derived from surgically resected specimens. We found a significant mutational landscape, including a high mutation burden and a unique mutational signature that were commonly observed in all of the investigated cases, suggesting that the workers had been exposed to one or several common strong mutagens. These data indicated a typical example of a common carcinogenic cause being reflected in the cancer genome as a common phenotype, and comprehensive genome analysis is useful for the exploration of environmental carcinogens. Based on these observations, we are promoting further analysis to understanding how these occupational cholangiocarcinoma have developed and progressed.