Te Paske, Iris B.A.W.Garcia-Pelaez, JoséSommer, Anna K.Matalonga, LeslieStarzynska, TeresaJakubowska, AnnaSolve-RD-GENTURIS groupvan der Post, Rachel S.Lubinski, JanOliveira, CarlaHoogerbrugge, Nicolinede Voer, Richarda M.2021-11-192021-11-192021Te Paske IBAW, Garcia-Pelaez J, Sommer AK, Matalonga L, Starzynska T, Jakubowska A; Solve-RD-GENTURIS group,, van der Post RS, Lubinski J, Oliveira C, Hoogerbrugge N, de Voer RM. A mosaic PIK3CA variant in a young adult with diffuse gastric cancer: case report. Eur J Hum Genet. 2021;29(9):1354-8. DOI: 10.1038/s41431-021-00853-61018-4813http://hdl.handle.net/10230/49020Hereditary 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.application/pdfeng© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41431-021-00853-6Cancer genomicsGastric cancerinfo:eu-repo/semantics/openAccess