Clinical and genomic characteristics of mucosal signet-ring cell carcinoma in Helicobacter pylori-uninfected stomach

Abstract

Background: Gastric cancer develops even in Helicobacter pylori(H. pylori)-uninfected patients and its typical histological feature is signet ring cell carcinoma (SRCC) within the mucosal layer. However, the biological characteristics of SRCC remain unclear. We aimed to clarify the pathological and genetic features of SRCC in H. pylori-uninfected patients. Methods: Seventeen H. pylori-uninfected patients with mucosal SRCCs were enrolled and their clinicopathological characteristics were compared with those of H. pylori-infected patients with mucosal SRCCs. Seven SRCCs without H. pylori-infected, including two invasive SRCCs, and seven H. pylori-infected SRCCs were subjected to a genetic analysis using next-generation sequencing. Results: H. pylori-uninfected patients with mucosal SRCCs revealed male dominancy and a significantly higher prevalence of smokers among them as compared with the H. pylori-infected patients with SRCC. A CDH1 mutation (frame shift indel) was detected in one H. pylori-uninfected cancer not only in the mucosal SRCC but also in the invasive portion. A TP53 mutation was detected in one SRCC without H. pylori-infected. In the control group, ARID1A and TP53 mutations were detected in one SRCC each. The C to A mutation, which is a characteristic smokinginduced mutation, was not found in any of the samples. Conclusions: Some SRCCs in H. pylori-uninfected patients may have a malignant potential similar to that of SRCCs in H. pylori-infected patients. Smoking may not be the main carcinogenic factor for the development of SRCCs among the H. pylori-uninfected patients.

Indolent feature of Helicobacter pylori-uninfected intramucosal signet ring cell carcinomas with CDH1 mutations

“…The methylation rates in intramucosal DGCs were generally low, although they tended to be higher than those in the adjacent normal mucosa (data not shown). Recent genetic analysis of Hp-uninfected DGC reported that CDH1 mutations were found in only one of seven cases, in contrast to the high prevalence of CDH1 mutations observed in our study [42]. The low amount of input DNA (10 ng in every case) and the long period of paraffin embedding (median 6 years) may have affected the quality of the analysis, resulting in a low frequency of detection of CDH1 mutations [45].…”

“…In addition to Hp infection, smoking has been reported to increase the risk of DGC compared to in non-smokers [39,40]. Previous studies reported that the prevalence of smoking was high in patients with Hp-uninfected DGCs [41,42]. However, SBS 4, the signature associated with smoking, was not observed in the present study (Fig.…”

TogoVar: A comprehensive Japanese genetic variation database

“…TogoVar is becoming recognized as shared infrastructure data. The purposes for its use are variant prioritization 34 , determination of whether a variant of interest is known or unknown 35 , and comparison of allele frequencies in TogoVar with those of disease groups or non-Japanese populations 36 , 37 .…”

The Incidence-Based Mortality and Survival Trends in Patients with Gastric Signet Ring Cell Carcinoma

“…Clinically, gastric SRC often inflicts the younger females, who are more susceptible to having distant metastasis, leading to poor survival outcomes [ 3 ]. Gastric SRC usually has more aggressive biological behavior than other subtypes of adenocarcinoma [ 4 ]. The overall prevalence of gastric cancer has gradually decreased in recent years, but the incidence of gastric SRC is still rising [ 5 ], accounting for 35%–45% of gastric adenocarcinoma cases recently [ 6 ].…”