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

Fusobacterium nucleatum(Fn) is frequently found in colorectal cancers (CRCs). High loads ofFnDNA are detected in CRC tissues with microsatellite instability-high (MSI-H), or with theCpGisland hypermethylation phenotype (CIMP).Fninfection 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 ofFnDNA are associated with MSI-H and L/E CRC respectively. We also show evidence thatFnproduces factors that induce gamma-H2AX, a hallmark of DNA double strand breaks (DSBs), in the infected cells.