A Japanese family of hereditary diffuse gastric cancer with a germline pathogenic variant of CTNN1A detected via comprehensive genome profiling.

CTNNA1 codes α-1 catenin, a molecule that functions in intercellular adhesion in combination with E-cadherin (coded by CDH1). A germline pathogenic variant (GPV) of CTNNA1 increases the risk of hereditary diffuse gastric cancer (HDGC); however, this GPV has not been reported in Japan. A 35-year-old Japanese man with an advanced gastric cancer underwent comprehensive genome profiling (CGP), which led to the detection of a CTNNA1 GPV (p.Q662*). His gastric cancer tissues demonstrated a loss of α-1 catenin expression. His mother with a history of gastric signet-ring cell carcinoma had undergone genetic counseling 2 years ago, because of her broad family history of young-onset gastric cancer. Then, she had undergone germline multigene panel testing (MGPT) that included CDH1 but not CTNNA1, and no GPV had been detected. Here, Japanese precision cancer medicine revealed a GPV of a gene rarely associated with HDGC, that could not be detected by common MGPTs.