Enrichment of T: A→A: T substitutions in the TP53 gene in esophageal carcinoma with high Fusobacterium burden

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Abstract
Exogenous lifestyle and environmental risk factors impact mutation burden in both benign and cancerous tissues. Moreover, interactions between the mucosa-associated microbiome and such genotoxic changes have been implicated in several cancer types. This study aimed to characterize the TP53 mutation spectrum in esophageal carcinoma (EC) with high amounts of Fusobacterium species. Quantitative PCR analysis of Pan-Fusobacterium species and Fusobacterium nucleatum was performed in 112 EC cases (89 squamous cell carcinomas [SCCs] and 23 adenocarcinomas). Results were correlated with TP53 mutation spectra and clinicopathological features. Both Pan-Fusobacterium species and F. nucleatum were significantly enriched in EC tissues compared with adjacent normal esophagus (both P < 0.001). The TP53 mutation spectrum in Pan-fusobacterium-high EC was characterized by a decrease in C: G→A: T and an increase in T: A→A: T substitutions (P < 0.001). Pan-fusobacterium-high EC was associated with male sex, tumors located in the upper or middle esophagus, and squamous cell histopathology. Cases of EC with detectable levels of Pan-Fusobacterium and F. nucleatum were also associated with more invasive tumors and more advanced cancer stages at diagnosis. These results suggest that EC with high numbers of Fusobacterium species was associated with a distinct mutation spectrum. Future studies should be conducted to investigate the mechanisms of how Fusobacterium species induce specific somatic mutations.
Funding Information
  • Japan Society for the Promotion of Science (22K08089)

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