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Fusobacterium nucleatum infection correlates with two types of microsatellite alterations in colorectal cancer and triggers DNA damage
Gut Pathogens ( IF 4.2 ) Pub Date : 2020-09-29 , DOI: 10.1186/s13099-020-00384-3
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 Martens , John M. Carethers

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.

中文翻译:

核梭形杆菌感染与大肠癌中两种类型的微卫星改变相关,并引发DNA损伤

在大肠癌(CRC)中经常发现核梭状芽胞杆菌(Fn)。在高微卫星不稳定性(MSI-H)或CpG岛超甲基化表型(CIMP)的CRC组织中检测到高负荷的Fn DNA。Fn感染也与CRC的炎性肿瘤微环境有关。CRC的一种亚型表现出与炎症相关的微卫星改变(IAMA),其特征是微卫星不稳定性低(MSI-L)和/或选定四核苷酸重复序列(EMAST)上微卫星改变的水平升高。在这里,我们描述了两个独立的CRC队列,其中Fn DNA的重负荷或中度负荷分别与MSI-H和L / E CRC相关。我们还显示证据表明Fn会在感染的细胞中产生诱导γ-H2AX(DNA双链断裂(DSBs)的标志)的因子。
更新日期:2020-09-30
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