Genetic analysis of a case of Helicobacter pylori-uninfected intramucosal gastric cancer in a family with hereditary diffuse gastric cancer
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Germline mutations in CDH1, encoding E-cadherin, are known to be the causative mechanism of hereditary diffuse gastric cancer (HDGC). We encountered two cases of gastric cancer in a Japanese family with HDGC. A 28-year-old man (Case 1) died of advanced gastric cancer. His younger sister aged 27 (Case 2) was diagnosed with intramucosal signet ring cell carcinoma (SRCC). Both had identical germline CDH1 mutations, but Case 1 was positive for Helicobacter pylori infection, whereas Case 2 was negative. Case 2 underwent total gastrectomy. Whole-exome sequencing of an intramucosal SRCC in Case 2 revealed seven somatic mutations including one in CDH1. The six non-CDH1 mutations were classified as non-driver mutations. Decreased expression of E-cadherin in intramucosal SRCC was confirmed by immunohistochemistry. Our report demonstrated that CDH1 mutation was the only active driver mutation in Helicobacter pylori-uninfected intramucosal SRCC.
KeywordsHereditary diffuse gastric cancer Helicobacter pylori-uninfected gastric cancer Signet ring cell carcinoma CDH1 E-cadherin
This research was supported by AMED under Grant Number JP18ck0106268 by National Cancer Center Research and Development Fund 28-A-1.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This study was approved by the ethics committee of Kyoto University.