Genome-wide analysis of DNA methylation in pseudomyxoma peritonei originated from appendiceal cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17641
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: The University of Tokyo
• Principal Investigator: Takane Kiyoko 東京大学, 医科学研究所, 助教 (60756112)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 腹膜偽粘液腫 / DNAメチル化 / KRAS / GNAS / オルガノイド

Outline of Final Research Achievements

Pseudomyxoma peritonei (PMP) is a disease characterized by progressive accumulation of intraperitoneal mucinous ascites caused by neoplasms in the abdominal cavity. Although the advancement in surgical treatment with intraoperative chemotherapy has improved the survival of patients with PMP, most of the patients need repeated treatment, which is lowering their quality of life. Therefore, the development of effective therapeutic drug(s) is a matter of pressing concern. Genetic analyses and expression profile analyses of PMP have clarified the frequent activation of GNAS and/or KRAS. However, the involvement of global epigenetic alterations in PMPs has not been reported. In this study, we performed genome-wide DNA methylation analysis using 15 appendiceal PMP samples. As a result, we clarified that the 15 PMPs are classified into at least two epigenotypes, unique methylation epigenotype (UME) and normal-like methylation epigenotype (NLME).

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

PMPは稀な腫瘍であるが、比較的早期に腫瘍が進展し、広範な腹膜転移をきたす。膵臓の乳管内乳頭粘液性腫瘍(IPMN)も、高頻度にKRASおよびGNASの変異が認められ、PMPと共通した機序で腫瘍が発生または進展している可能性が高い。このことは、PMPの発がんメカニズム解明と、新たなバイオマーカー、治療標的分子の探索により、がんの転移の抑制や、IPMNや腹膜播種などの治療に役立つ可能性があることを意味している。