Genetic analysis of a case of Helicobacter pylori -uninfected intramucosal gastric cancer in a family with hereditary diffuse gastric cancer

AbstractGermline mutations inCDH1, 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 germlineCDH1 mutations, but Case 1 was positive forHelicobacter 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 inCDH1. 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 thatCDH1 mutation was the only active driver mutation inHelicobacter pylori-uninfected intramucosal SRCC.
Source: Gastric Cancer - Category: Gastroenterology Source Type: research