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

Vogelaar IP, van der Post RS, van Krieken JHJ, L Spruijt, van Zelst-Stams WA, Kets CM, J Lubinski, A Jakubowska, U Teodorczyk, Aalfs CM, van Hest LP, H Pinheiro, C Oliveira, Jhangiani SN, Muzny DM, Gibbs RA, Lupski JR, J de Ligt, Vissers LELM, A HoischenC Gilissen, M van de Vorst, Goeman JJ, Schackert HK, Ranzani GN, V Molinaro, Gómez García EB, Hes FJ, E Holinski-Feder, Maurizio Genuardi, Ausems MGEM, Sijmons RH, A Wagner, van der Kolk LE, I Bjørnevoll, H Høberg-Vetti, van Kessel AG, Kuiper RP, Ligtenberg MJL, N Hoogerbrugge*

*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivistaArticolo

22 Citazioni (Scopus)

Abstract

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 originaleInglese
pagine (da-a)1246-1252
Numero di pagine7
RivistaEuropean Journal of Human Genetics
Numero di pubblicazione11
DOI
Stato di pubblicazionePubblicato - 2017

All Science Journal Classification (ASJC) codes

  • Genetica
  • Genetica (clinica)

Keywords

  • gastric cancer

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