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.
Highlights
In ~10% of the gastric cancer (GC) cases familial aggregation is observed [1]
The patient tested negative for H. pylori infection and no other coexisting disorders or congenital abnormalities were reported
We present the case of a woman with earlyonset diffuse gastric cancer (DGC) in whom neither targeted CDH1 and CTNNA1 variant screening, nor a previous whole-exome sequencing (WES) analysis provided a genetic diagnosis
Summary
In ~10% of the gastric cancer (GC) cases familial aggregation is observed [1]. Two monogenic GC-associated syndromes have been described so far: (i) Hereditary Diffuse Gastric Cancer syndrome (HDGC; MIM 137215) [2], Members of the Solve-RD-GENTURIS group are listed below Acknowledgements. HDGC is associated with germline deleterious variants in CDH1 and CTNNA1. Deleterious variants in CDH1 or CTNNA1 are identified in only 10-40% of families fulfilling HDGC clinical criteria [2, 4, 5]. A large proportion of clinically and pathologically confirmed HDGC families and individuals developing diffuse gastric cancer (DGC) at very young age remain genetically unresolved, raising the need for research on novel inherited predisposing factors. Case of a 25-year-old female with DGC, in whom a mosaic PIK3CA variant was identified in leukocyte-derived DNA by re-analysis of whole-exome sequencing (WES) data by the SOLVE-RD consortium
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
