Germline whole-exome sequencing identifies CTNND1 as a candidate gene for hereditary gastric cancer in a large Brazilian cohort.

Rare germline CTNND1 variant (a CDH1 partner); diffuse and signet-ring cell gastric tumours.

First Brazilian germline whole-exome sequencing study (126 patients) dedicated to hereditary gastric cancer predisposition. Among the 11 cases with an identified predisposition syndrome, BRCA2 was the most frequently mutated (27.3 %). Sequencing highlighted candidate genes, including FBXO24 and above all CTNND1, the latter with emerging evidence of association with gastric predisposition. TCGA somatic data showed that diffuse gastric tumours and signet-ring cell adenocarcinomas with CTNND1 mutations exhibited high microsatellite instability and high mutation count.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The biological link of CTNND1 (p120-catenin) with CDH1, the major hereditary diffuse gastric cancer gene, makes the hypothesis plausible. But this is a candidate gene supported by a single rare germline variant, without segregation or functional proof — hence a cautious score. Worth following, but not yet to be presented as a validated predisposition gene in clinic.

Analysis by Dr Thibaut Benquey