Pathological and physiological functions of DNA methylation in cancer

• Project/Area Number: 25640079
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor diagnostics
• Research Institution: Sapporo Medical University
• Principal Investigator: MARUYAMA Reo 札幌医科大学, 医学部, 准教授 (60607985)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: DNA methylation / DNAメチル化 / 大腸癌

Outline of Final Research Achievements

In this study, we aimed to ascertain the pathological and physiological implications of aberrant DNA methylation, which is universally observed over the course of carcinogenesis. We performed integrated analysis of publicly available DNA methylation data and our own clinical datasets. We identified regions where DNA methylations were consistently observed in various tumors. Genomic distribution of the regions suggests that three-dimensional chromatin structures are involved in this epigenomic change. Through a similar analysis, we also identified 33 genes that are silenced by DNA methylation in normal tissues, whereas overexpressed in a subset of cancer probably due to DNA de-methylation. We are currently examining the clinical and functional implications of these genes.

Research Products

• [Journal Article] Age- and pregnancy-associated DNA methylation changes in mammary epithelial cells (2015)
  • Author(s): Huh SJ, Clement K, Jee D, Merlini A, Choudhury S, Maruyama R, Yoo R, Chytil A, Boyle P, Ran FA, Moses HL, Barcellos-Hoff MH, Jackson-Grusby L, Meissner A, Polyak K
  • Journal Title: Stem Cell Reports Volume: 4 Issue: 2 Pages: 297-311
  • DOI: 10.1016/j.stemcr.2014.12.009
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of DNA methylation in bowel lavage fluid for detection of colorectal cancer (2014)
  • Author(s): Harada T, Yamamoto E, Yamano HO, Nojima M, Maruyama R, Kumegawa K, Ashida M, Yoshikawa K, Kimura T, Harada E, Takagi R, Tanaka Y, Aoki H, Nishizono M, Nakaoka M, Tsuyada A, Niinuma T, Kai M, Shimoda K, Shinomura Y, Sugai T, Imai K, Suzuki H
  • Journal Title: Cancer Prevention Research Volume: 7 Pages: 1002-1010
  • Peer Reviewed
• [Journal Article] JARID1B is a luminal lineage-driving oncogene in breast cancer (2014)
  • Author(s): Yamamoto S, Wu Z, Russnes HG, Takagi S, Peluffo G, Vaske C, Zhao X, Moen Vollan HK, Maruyama R, Ekram MB, Sun H, Kim JH, Carver K, Zucca M, Feng J, Almendro V, Bessarabova M, Rueda OM, Nikolsky Y, Caldas C, Liu XS, Polyak K
  • Journal Title: Cancer Cell Volume: 25 Issue: 6 Pages: 762-777
  • DOI: 10.1016/j.ccr.2014.04.024
  • Peer Reviewed
• [Presentation] Genome-wide identification of lincRNAs epigenetically silenced by DNA methylation in colon cancer. (2014)
  • Author(s): Igarashi T, Kumegawa K, Maruyama R, Yamamoto E, Tsuyada A, Suzuki R, Niinuma T, Kai M, Yamano H, Sugai T, Tokino T, Shinomura Y, Suzuki H.
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27