Fusobacterium nucleatum infection correlates with two types of microsatellite alterations in colorectal cancer and triggers DNA damage
Yoshiki Okita, Minoru Koi, Koki Takeda, Ryan Ross, Bhramar Mukherjee, Erika Koeppe, Elena M. Stoffel, Joseph A. Galanko, Amber N. McCoy, Temitope O. Keku, Yoshinaga Okugawa, Takahito Kitajima, Yuji Toiyama, Eric C. Martens, John M. Carethers
Abstract
Abstract 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.