AIMS: Mutations of the E-cadherin gene (CDH1) result in dominantly inherited hereditary diffuse gastric cancer (HDGC). We report a study in the first family diagnosed with HDGC in Spain, examining the presence of mutations in the CDH1 gene. METHODS: The presence of mutations was studied by direct sequencing of all CDH1 exons. Immunohistochemical analysis with specific antibodies was used to detect the expression of E-cadherin in normal and tumour tissue. RESULTS: A novel 1610delC mutation in exon 11 has been found in a Spanish family diagnosed with HDGC. This mutation generates a premature stop codon at position 1667 giving rise to a truncated protein that lacks the transmembrane and beta-catenin-binding domains. The presence of a 1610delC germline mutation was confirmed in three family members diagnosed with diffuse gastric cancer, and also in six asymptomatic members. Of note, the diffuse gastric cancer coexisted with a gastric lymphoma in the proband. Furthermore, immunohistochemical analyses of tumour tissue showed the complete absence of E-cadherin in the proband, revealing a second genetic hit at the CDH1 locus. CONCLUSIONS: We have identified a HDGC family in Spain that carries a novel germline truncating mutation in the CDH1 gene.
AIMS: Mutations of the E-cadherin gene (CDH1) result in dominantly inherited hereditary diffuse gastric cancer (HDGC). We report a study in the first family diagnosed with HDGC in Spain, examining the presence of mutations in the CDH1 gene. METHODS: The presence of mutations was studied by direct sequencing of all CDH1 exons. Immunohistochemical analysis with specific antibodies was used to detect the expression of E-cadherin in normal and tumour tissue. RESULTS: A novel 1610delC mutation in exon 11 has been found in a Spanish family diagnosed with HDGC. This mutation generates a premature stop codon at position 1667 giving rise to a truncated protein that lacks the transmembrane and beta-catenin-binding domains. The presence of a 1610delC germline mutation was confirmed in three family members diagnosed with diffuse gastric cancer, and also in six asymptomatic members. Of note, the diffuse gastric cancer coexisted with a gastric lymphoma in the proband. Furthermore, immunohistochemical analyses of tumour tissue showed the complete absence of E-cadherin in the proband, revealing a second genetic hit at the CDH1 locus. CONCLUSIONS: We have identified a HDGC family in Spain that carries a novel germline truncating mutation in the CDH1 gene.
Authors: Giovanni Corso; Valentina Tagliaferri; Giulia Massari; Antonio Cioffi; Elisabetta Maria Cristina Rossi; Paolo Veronesi; Francesca Magnoni Journal: Fam Cancer Date: 2022-07-27 Impact factor: 2.446