Chromosomal instability induced by DNA demethylation alterations

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462035
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Jichi Medical University
• Principal Investigator: Suzuki Koichi 自治医科大学, 医学部, 講師 (70332369)
• Co-Investigator(Kenkyū-buntansha): RIKIYAMA Toshiki 自治医科大学, 医学部, 教授 (80343060)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: Satelliteα / 遺伝子修飾異常 / non-cording RNA / セントロメア / 染色体不安定性 / 染色体分配 / 加齢 / ゲノム損傷

Outline of Final Research Achievements

Impairment of stability in chromosomal structure facilitates abnormal segregation of chromosome, increasing the risk of carcinogenesis. Segregation is managed by appropriate methylation, leading to heterochromatin structure at centromere. Insufficient methylation such as demethylation fails to heterochromatin due to overexpression of satellite alpha transcript (SatA), which is the non-coding RNA transcribed from satellite alpha sequences at centromere. We showed SatA expression was increased in colorectal cancer, in which satellite sequences were demethylated, resulting in chromosomal instability. We verified this machinery in vitro. The lentiviral vector expressing human SatA was constructed and transduced in cultured cells. Copy number alterations were observed at several chromosomes in transduced cells but not in mock cells. Alterations were frequently seen at chromosome 8q and 20q, which is consistent with the results in clinical specimens.

Free Research Field

腫瘍外科