Fusobacterium nucleatum infection correlates with two types of microsatellite alterations in colorectal cancer and triggers DNA damage

Gut Pathogens

Ryan Ross¹  Bhramar Mukherjee¹  Yuji Toiyama²  Yoshinaga Okugawa²  Takahito Kitajima²  Eric Martens³  Yoshiki Okita⁴  Erika Koeppe⁴  Elena M. Stoffel⁴  Minoru Koi⁴  Koki Takeda⁴  John M. Carethers⁵  Joseph A. Galanko⁶  Temitope O. Keku⁶  Amber N. McCoy⁶ 

[1] Department of Biostatistics School of Public Health, University of Michigan, Ann Arbor, MI, USA;Department of Gastrointestinal and Pediatric Surgery, Graduate School of Medicine, Mie University, Mie, Japan;Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA;Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA;Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA;Department of Human Genetics and Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA;Division of Gastroenterology and Hepatology, Departments of Medicine & Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;

关键词: Fusobacterium nucleatum;    Colorectal cancer;    Microsatellite instability;    CpG;    MSI-L;    EMAST;    MSH3;    Mismatch repair;    Inflammation;   

DOI  :  10.1186/s13099-020-00384-3

来源: Springer

【 摘 要 】

Fusobacterium nucleatum (Fn) is frequently found in colorectal cancers (CRCs). High loads of Fn DNA are detected in CRC tissues with microsatellite instability-high (MSI-H), or with the CpG island hypermethylation phenotype (CIMP). Fn infection is also associated with the inflammatory tumor microenvironment of CRC. A subtype of CRC exhibits inflammation-associated microsatellite alterations (IAMA), which are characterized by microsatellite instability-low (MSI-L) and/or an elevated level of microsatellite alterations at selected tetra-nucleotide repeats (EMAST). Here we describe two independent CRC cohorts in which heavy or moderate loads of Fn DNA are associated with MSI-H and L/E CRC respectively. We also show evidence that Fn produces factors that induce γ-H2AX, a hallmark of DNA double strand breaks (DSBs), in the infected cells.

【 授权许可】

CC BY