{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:58:02Z","timestamp":1791356282132,"version":"4.3.1"},"reference-count":30,"publisher":"BMJ","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:sec>\n                  <jats:title>Background:<\/jats:title>\n                  <jats:p>The cell surface glycoprotein E-cadherin (<jats:italic>CDH1<\/jats:italic>) is a key regulator of adhesive properties in epithelial cells. Germline mutations in <jats:italic>CDH1<\/jats:italic> are well established as the defects underlying hereditary diffuse gastric cancer (HDGC) syndrome, and an increased risk of lobular breast cancer (LBC) has been described in HDGC kindreds. However, germline <jats:italic>CDH1<\/jats:italic> mutations have not been described in patients with LBC in non-HDGC families. This study aimed to investigate the frequency of germline <jats:italic>CDH1<\/jats:italic> mutations in patients with LBC with early onset disease or family histories of breast cancer without DGC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>Germline DNA was analysed in 23 women with invasive lobular or mixed ductal and lobular breast cancers who had at least one close relative with breast cancer or had themselves been diagnosed before the age of 45 years, had tested negative for a germline <jats:italic>BRCA1<\/jats:italic> or <jats:italic>BRCA2<\/jats:italic> mutation, and reported no personal or family history of diffuse gastric cancer. The full coding sequence of <jats:italic>CDH1<\/jats:italic> including splice junctions was amplified using PCR and screened for mutations using DHPLC and sequencing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>A novel germline <jats:italic>CDH1<\/jats:italic> truncating mutation in the extracellular portion of the protein (517insA) was identified in one woman who had LBC at the age of 42 years and a first degree relative with invasive LBC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>Germline <jats:italic>CDH1<\/jats:italic> mutations can be associated with invasive LBC in the absence of diffuse gastric cancer. The finding, if confirmed, may have implications for management of individuals at risk for this breast cancer subtype. Clarification of the cancer risks in the syndrome is essential.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2007.051268","type":"journal-article","created":{"date-parts":[[2007,7,27]],"date-time":"2007-07-27T21:27:41Z","timestamp":1185571661000},"page":"726-731","source":"Crossref","is-referenced-by-count":163,"title":["Germline E-cadherin mutations in familial lobular breast 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