Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing
| Autor: | Carla Oliveira, Roland P. Kuiper, Hildegunn Høberg-Vetti, James R. Lupski, Encarna B. Gomez Garcia, Margreet G. E. M. Ausems, Christian Gilissen, Liesbeth Spruijt, Elke Holinski-Feder, C. Marleen Kets, Urszula Teodorczyk, Jelle J. Goeman, Rachel S. van der Post, Ad Geurts van Kessel, Anja Wagner, Alexander Hoischen, Anna Jakubowska, Wendy A. G. van Zelst-Stams, Rolf H. Sijmons, Cora M. Aalfs, Nicoline Hoogerbrugge, Maartje van de Vorst, Marjolijn J. L. Ligtenberg, Maurizio Genuardi, Shalini N. Jhangiani, Jan Lubinski, Lisenka E.L.M. Vissers, Frederik J. Hes, Inga Bjørnevoll, J. Han van Krieken, Hugo Pinheiro, Hans K. Schackert, Joep de Ligt, Ingrid P. Vogelaar, Guglielmina Nadia Ranzani, Donna M. Muzny, Liselotte P. van Hest, Richard A. Gibbs, Lizet E. van der Kolk, Valeria Molinaro |
|---|---|
| Přispěvatelé: | CCA - Cancer biology and immunology, Human genetics, Medical Genetics, Human Genetics, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), Klinische Genetica, Clinical Genetics, Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Candidate gene Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] VARIANTS Gene mutation Bioinformatics Germline COLORECTAL-CANCER 0302 clinical medicine CDH1 MUTATIONS Stomach Neoplasms/diagnosis HISTORY Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] Genetics(clinical) Exome Early Detection of Cancer DIFFUSE Genetics (clinical) Exome sequencing RISK Genetics Medicine(all) Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] Middle Aged Cadherins 3. Good health Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] Sequence Analysis DNA/methods 030220 oncology & carcinogenesis Female Genetic Testing/methods Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] Adult medicine.medical_specialty MUTATION CARRIERS Biology Article CLASSIFICATION 03 medical and health sciences Germline mutation SDG 3 - Good Health and Well-being Stomach Neoplasms HELICOBACTER-PYLORI Antigens CD RESOURCE Molecular genetics Genetic predisposition medicine Journal Article Humans Genetic Predisposition to Disease Genetic Testing Germ-Line Mutation Aged Settore MED/06 - ONCOLOGIA MEDICA Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] gastric cancer Cadherins/genetics Sequence Analysis DNA 030104 developmental biology Early Detection of Cancer/methods exome |
| Zdroj: | European Journal of Human Genetics, 25, 11, pp. 1246-1252 European Journal of Human Genetics, 25(11), 1246. Nature Publishing Group European Journal of Human Genetics, 25(11), 1246-1252. Nature Publishing Group European journal of human genetics, 25(11), 1246-1252. Nature Publishing Group European Journal of Human Genetics, 25, 1246-1252 European Journal of Human Genetics Vogelaar, I P, Van Der Post, R S, Van Krieken, J H J M, Spruijt, L, Van Zelst-Stams, W A G, Kets, C M, Lubinski, J, Jakubowska, A, Teodorczyk, U, Aalfs, C M, Van Hest, L P, Pinheiro, H, Oliveira, C, Jhangiani, S N, Muzny, D M, Gibbs, R A, Lupski, J R, De Ligt, J, Vissers, L E L M, Hoischen, A, Gilissen, C, Van De Vorst, M, Goeman, J J, Schackert, H K, Ranzani, G N, Molinaro, V, García, E B G, Hes, F J, Holinski-Feder, E, Genuardi, M, Ausems, M G E M, Sijmons, R H, Wagner, A, Van Der Kolk, L E, Bjørnevoll, I, Høberg-Vetti, H, Van Kessel, A G, Kuiper, R P, Ligtenberg, M J L & Hoogerbrugge, N 2017, ' Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing ', European Journal of Human Genetics, vol. 25, no. 11, pp. 1246-1252 . https://doi.org/10.1038/ejhg.2017.138 European Journal of Human Genetics, 25(11), 1246-1252 |
| ISSN: | 1018-4813 |
| DOI: | 10.1038/ejhg.2017.138 |
| Popis: | Contains fulltext : 182216.pdf (Publisher’s version ) (Open Access) 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink