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Author(s): Weren R
Van Der Post R
Vogelaar I
Han Van Krieken J
Spruijt L
Lubinski J
Jakubowska A
Teodorczyk U
Aalfs C
Van Hest L
Oliveira C
Kamping E
Schackert H
Ranzani G
García E
Hes F
Holinski-Feder E
Genuardi M
Ausems M
Sijmons R
Wagner A
Van Der Kolk L
Cats A
Bjørnevoll I
Hoogerbrugge N
Ligtenberg M
Title: Role of germline aberrations affecting CTNNA1, MAP3K6 and MYD88 in gastric cancer susceptibility
Publisher: British Medical Association
Issue Date: 2018
Abstract: 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.
Source: Journal of Medical Genetics, vol.55(10), p. 669-674
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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