@article{afda09cf7b6c45de9b7e64eb1153c916,
title = "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.",
keywords = "Adult, Class I Phosphatidylinositol 3-Kinases/genetics, Female, Humans, Mosaicism, Mutation, Missense, Stomach Neoplasms/genetics, Whole Exome Sequencing",
author = "{te Paske}, I.B.A.W. and J. Garcia-Pelaez and A.K. Sommer and L. Matalonga and T. Starzynska and A. Jakubowska and L. Valle and G. Capella and S. Aretz and E. Holinski-Feder and V. Steinke-Lange and A. Laner and E. Schr{\"o}ck and A. Rump and M. Ligtenberg and A. Hoischen and N. Geverink and D.G. Evans and M. Tischkowitz and S. Laurie and {van der Post}, R.S. and J. Lubinski and C. Oliveira and N. Hoogerbrugge and {de Voer}, R.M.",
note = "Funding Information: Acknowledgements The authors would like to thank SOLVE-RD for the infrastructure and in-depth discussions on strategies for the reanalyses of genomic data for disease gene identification. This research is supported (not financially) by the European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS)—Project ID No 739547. ERN GENTURIS is partly co-funded by the European Union within the framework of the Third Health Programme ERN-2016— Framework Partnership Agreement 2017–2021. Funding Information: 11Catalan Institute of Oncology, IDIBELL, Barcelona, Spain; 12MGZ-Center of Medical Genetics, Munich, Germany; 13Institute for Clinical Genetics, Technical University Dresden, Dresden, Germany; 14Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands; 15Department of Human Genetics, Rad-boud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands; 16Department of Urology, Radboud University Medical Center, Nijmegen, the Netherlands; 17Manchester Centre for Genomic Medicine, Manchester, UK; 18Department of Medical Genetics, University of Cambridge, Cambridge, UK; 19CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain Funding The Solve-RD project has received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation programme under grant agreement No 779257. The research work at i3S/Ipatimup is supported by the European Regional Development Fund (ERDF) through COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT/ Minist{\'e}rio da Ci{\^e}ncia, Tecnologia e Inova{\c c}{\~a}o in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) and Project Ref. POCI-01-0145-FEDER-030164. Data was reanalysed using the RD‐Connect Genome‐Phenome Analysis Platform, which received funding from EU projects RD‐Connect, Solve-RD and EJP-RD (grant numbers FP7 305444, H2020 779257, H2020 825575), Instituto de Salud Carlos III (grant numbers PT13/0001/0044, PT17/ 0009/0019; Instituto Nacional de Bioinform{\'a}tica, INB) and ELIXIR Implementation Studies. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = jun,
day = "1",
doi = "10.1038/s41431-021-00853-6",
language = "English",
volume = "29",
pages = "1354--1358",
journal = "European Journal of Human Genetics",
issn = "1018-4813",
publisher = "Springer Nature",
number = "9",
}
