A mosaic PIK3CA variant in a young adult with diffuse gastric cancer: case report

Abstract

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.

Fig. 1. Mosaic PIK3CA c.3140A>G variant found in leukocyte DNA of the proband.

A Screenshot of the Integrative Genomics Viewer. Alternative alleles at PIK3CA c.3140 position are marked. Variant details are shown in the panel on the right. B Screenshot of one outcome of the in triplicate smMIP screened leukocyte-derived DNA from the proband. The PIK3CA (c.3140A>G; p.(His1047Arg)) variant is marked in red. C Screenshot of individual reads in smMIP analysis. Alternative alleles at PIK3CA c.3140 position are marked in red.