Clinical implications of CTNNA1 germline mutations in asymptomatic carriers

Gastric Cancer. 2019 Jul;22(4):899-903. doi: 10.1007/s10120-018-00907-7. Epub 2018 Dec 4.

Abstract

In 2017, we implemented CTNNA1 germline analysis in probands suspected of having hereditary diffuse gastric cancer. Here, we report the results from a retrospective series of 41 cases, including the identification of a new family with a CTNNA1 mutation and the first prophylactic total gastrectomy in an asymptomatic carrier after a normal upper endoscopy. Diffuse gastric cancer foci with loss of catenin alpha-1 expression were seen in the resected tissue, suggesting that CTNNA1 and CDH1 germline mutations behave in a similar manner. Life-changing prophylactic total gastrectomy should therefore also be considered in CTNNA1 mutation carriers.

Keywords: CDH1; CTNNA1; Diffuse gastric cancer; Hereditary cancer; Signet-ring cell.

MeSH terms

  • Adult
  • Asymptomatic Diseases / therapy*
  • Carcinoma, Signet Ring Cell / genetics*
  • Carcinoma, Signet Ring Cell / metabolism
  • Carcinoma, Signet Ring Cell / pathology
  • Carcinoma, Signet Ring Cell / surgery
  • Female
  • Follow-Up Studies
  • Gastrectomy
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Prognosis
  • Retrospective Studies
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • alpha Catenin / genetics*
  • alpha Catenin / metabolism

Substances

  • CTNNA1 protein, human
  • alpha Catenin