TY - JOUR T1 - Role of germline aberrations affecting <em>CTNNA1</em>, <em>MAP3K6</em> and <em>MYD88</em> in gastric cancer susceptibility JF - Journal of Medical Genetics JO - J Med Genet DO - 10.1136/jmedgenet-2017-104962 SP - jmedgenet-2017-104962 AU - Robbert D A Weren AU - Rachel S van der Post AU - Ingrid P Vogelaar AU - J Han van Krieken AU - Liesbeth Spruijt AU - Jan Lubinski AU - Anna Jakubowska AU - Urszula Teodorczyk AU - Cora M Aalfs AU - Liselotte P van Hest AU - Carla Oliveira AU - Eveline J Kamping AU - Hans K Schackert AU - Guglielmina N Ranzani AU - Encarna B Gómez García AU - Frederik J Hes AU - Elke Holinski-Feder AU - Maurizio Genuardi AU - Margreet G E M Ausems AU - Rolf H Sijmons AU - Anja Wagner AU - Lizet E van der Kolk AU - Annemieke Cats AU - Inga Bjørnevoll AU - Nicoline Hoogerbrugge AU - Marjolijn J L Ligtenberg Y1 - 2018/01/12 UR - http://jmg.bmj.com/content/early/2018/01/12/jmedgenet-2017-104962.abstract N2 - Background In approximately 10% of all gastric cancer (GC) cases, a heritable cause is suspected. A subset of these cases have a causative germline CDH1 mutation; however, in most cases the cause remains unknown. Our objective was to assess to what extent these remaining cases may be explained by germline mutations in the novel candidate GC predisposing genes CTNNA1, MAP3K6 or MYD88.Methods We sequenced a large cohort of unexplained young and/or familial patients with GC (n=286) without a CDH1germline mutation for germline variants affecting CTNNA1, MAP3K6 and MYD88 using a targeted next-generation sequencing approach based on single-molecule molecular inversion probes.Results Predicted deleterious germline variants were not encountered in MYD88, but recurrently observed in CTNNA1 (n=2) and MAP3K6 (n=3) in our cohort of patients with GC. In contrast to deleterious variants in CTNNA1, deleterious variants in MAP3K6 also occur frequently in the general population.Conclusions Based on our results MAP3K6 should no longer be considered a GC predisposition gene, whereas deleterious CTNNA1 variants are confirmed as an infrequent cause of GC susceptibility. Biallelic MYD88 germline mutations are at most a very rare cause of GC susceptibility as no additional cases were identified. ER -