Analysis of gene mutation in early sporadic diffuse-type gastric cancer based on Helicobacter pylori infection status through whole-exome sequencing

Aims Previous reports have suggested that Helicobacter pylori (HP)-infected diffuse-type gastric cancer (DGC) shows more aggresive features, compared with HP-uninfected DGC. However, the genomic feature of early DGCs based on HP status has been largely unknown. We aimed to discover genomic differences between HP-uninfected and HP-infected early DGC.

Methods We conducted whole-exome sequencing analysis of 27 HP-uninfected and 36 HP-infected early DGC samples. [1] [2]

Results HP-infected DGCs exhibited an increased single nucleotide variant burden (HP-exposed DGCs; 1.97 and HP-naïve DGCs; 1.09 per megabase; p = 0.0003). CDH1 was most highly recurrent mutation in both groups (HP-uninfected:65.4%, HP-infected:69.7%). RHOA–ARHGAP pathway was exclusively misregulated in HP–infected DGCs (p=0.0167). HP-infected DGCs significantly frequent chromosomal aberration of gain at 8p (p<0.0001) and 8q (p<0.0001).

Conclusions This study reveals that HP-uninfected and HP-infected DGCs develop along different molecular pathways, which provide an explanation for indolent features of HP-uninfected DGCs.

Conflicts of interest

Authors do not have any conflict of interest to disclose.

• 1 Nikaido M, Kakiuchi N, Miyamoto S. et al. Indolent feature of Helicobacter pylori-uninfected intramucosal signet ring cell carcinomas with CDH1 mutations. Gastric Cancer 2021; 24: 1102-1114
• 2 Horiuchi Y, Fujisaki J, Yamamoto N. et al. Biological behavior of the intramucosal Helicobacter pylori-negative undifferentiated-type early gastric cancer: comparison with Helicobacter pylori-positive early gastric cancer. Gastric Cancer 2016; 19: 160-165

Publication History

Article published online:
14 April 2023