Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing

Maurizio Genuardi, Ingrid P. Vogelaar, Rachel S. Van Der Post, J Han J.M. Van Krieken, Liesbeth Spruijt, Wendy A.G. Van Zelst-Stams, C Marleen Kets, Jan Lubinski, Anna Jakubowska, Urszula Teodorczyk, Cora M. Aalfs, Liselotte P. Van Hest, Hugo Pinheiro, Carla Oliveira, Shalini N. Jhangiani, Donna M. Muzny, Richard A. Gibbs, James R. Lupski, Joep De Ligt, Lisenka E.L.M. VissersAlexander Hoischen, Christian Gilissen, Maartje Van De Vorst, Jelle J. Goeman, Hans K. Schackert, Guglielmina N. Ranzani, Valeria Molinaro, Encarna B. Gómez García, Frederik J. Hes, Elke Holinski-Feder, Margreet G.E.M. Ausems, Rolf H. Sijmons, Anja Wagner, Lizet E. Van Der Kolk, Inga Bjørnevoll, Hildegunn Høberg-Vetti, Ad Geurts Van Kessel, Roland P. Kuiper, Marjolijn J.L. Ligtenberg, Nicoline Hoogerbrugge

Risultato della ricerca: Contributo in rivistaArticolo in rivista

20 Citazioni (Scopus)


Recognition of individuals with a genetic predisposition to gastric cancer (GC) enables preventive measures. However, the underlying cause of genetic susceptibility to gastric cancer remains largely unexplained. We performed germline whole-exome sequencing on leukocyte DNA of 54 patients from 53 families with genetically unexplained diffuse-type and intestinal-type GC to identify novel GC-predisposing candidate genes. As young age at diagnosis and familial clustering are hallmarks of genetic tumor susceptibility, we selected patients that were diagnosed below the age of 35, patients from families with two cases of GC at or below age 60 and patients from families with three GC cases at or below age 70. All included individuals were tested negative for germline CDH1 mutations before or during the study. Variants that were possibly deleterious according to in silico predictions were filtered using several independent approaches that were based on gene function and gene mutation burden in controls. Despite a rigorous search, no obvious candidate GC predisposition genes were identified. This negative result stresses the importance of future research studies in large, homogeneous cohorts.
Lingua originaleEnglish
pagine (da-a)1246-1252
Numero di pagine7
RivistaEuropean Journal of Human Genetics
Stato di pubblicazionePubblicato - 2017


  • gastric cancer

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