Hereditary diffuse gastric cancer (HDGC) is associated with germline deleterious variants in CDH1 and CTNNA1. The majority of HDGC-suspected patients are still genetically unresolved, raising the need for identification of novel HDGC predisposing genes. Under the collaborative environment of the SOLVE-RD consortium, re-analysis of whole-exome sequencing data from unresolved gastric cancer cases (n = 83) identified a mosaic missense variant in PIK3CA in a 25-year-old female with diffuse gastric cancer (DGC) without familial history for cancer. The variant, c.3140A>G p.(His1047Arg), a known cancer-related somatic hotspot, was present at a low variant allele frequency (18%) in leukocyte-derived DNA. Somatic variants in PIK3CA are usually associated with overgrowth, a phenotype that was not observed in this patient. This report highlights mosaicism as a potential, and understudied, mechanism in the etiology of DGC.

遗传性弥漫性胃癌 (HDGC) 与CDH1和CTNNA1种系有害变异相关。大多数 HDGC 疑似患者的遗传问题仍未解决，因此需要鉴定新的 HDGC 易感基因。在 SOLVE-RD 联盟的协作环境下，对未解决的胃癌病例 ( n = 83)的全外显子组测序数据进行重新分析，在一名患有弥漫性胃癌的 25 岁女性中发现了PIK3CA 中的嵌合错义变异( DGC）没有癌症家族史。该变体 c.3140A>G p.(His1047Arg) 是一种已知的癌症相关体细胞热点，在白细胞来源的 DNA 中以低变体等位基因频率 (18%) 存在。PIK3CA的体细胞变异通常与过度生长相关，但在该患者中未观察到这种表型。本报告强调嵌合现象是 DGC 病因学中一种潜在的、尚未得到充分研究的机制。