Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing
Publication year
2017Author(s)
Source
European Journal of Human Genetics, 25, 11, (2017), pp. 1246-1252ISSN
Publication type
Article / Letter to editor

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Organization
Human Genetics
Pathology
Internal Medicine
Health Evidence
Journal title
European Journal of Human Genetics
Volume
vol. 25
Issue
iss. 11
Page start
p. 1246
Page end
p. 1252
Subject
Radboudumc 14: Tumours of the digestive tract RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 17: Women's cancers RIHS: Radboud Institute for Health Sciences; Radboudumc 2: Cancer development and immune defence RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 6: Metabolic Disorders RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience; Radboudumc 9: Rare cancers RIHS: Radboud Institute for Health SciencesAbstract
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.
This item appears in the following Collection(s)
- Academic publications [227425]
- Electronic publications [107155]
- Faculty of Medical Sciences [86157]
- Open Access publications [76288]
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