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<p>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 <i>TP53</i> mutation spectrum in esophageal carcinoma (EC) with high amounts of <i>Fusobacterium</i> species. Quantitative PCR analysis of Pan-<i>Fusobacterium</i> species and <i>Fusobacterium nucleatum</i> was performed in 112 EC cases (89 squamous cell carcinomas [SCCs] and 23 adenocarcinomas). Results were correlated with <i>TP53</i> mutation spectra and clinicopathological features. Both Pan-<i>Fusobacterium</i> species and <i>F. nucleatum</i> were significantly enriched in EC tissues compared with adjacent normal esophagus (both <i>P</i> &lt; 0.001). The <i>TP53</i> mutation spectrum in Pan-<i>fusobacterium-</i>high EC was characterized by a decrease in C: G→A: T and an increase in T: A→A: T substitutions (<i>P</i> &lt; 0.001). Pan<i>-fusobacterium</i>-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-<i>Fusobacterium</i> and <i>F. nucleatum</i> were also associated with more invasive tumors and more advanced cancer stages at diagnosis. These results suggest that EC with high numbers of <i>Fusobacterium</i> species was associated with a distinct mutation spectrum. Future studies should be conducted to investigate the mechanisms of how <i>Fusobacterium</i> species induce specific somatic mutations.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月10日

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  • Tomomitsu Tahara,
  • Takuya Shijimaya,
  • Jumpei Yamazaki,
  • Tsubasa Shimogama,
  • Sanshiro Kobayashi,
  • Naohiro Nakamura,
  • Yu Takahashi,
  • Takashi Tomiyama,
  • Toshiro Fukui,
  • Tomoyuki Shibata,
  • Makoto Naganuma

摘要

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.