{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:35:33Z","timestamp":1789788933384,"version":"4.0.1"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,2,3]],"date-time":"2014-02-03T00:00:00Z","timestamp":1391385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:p>Germline inactivation of the E\u2010cadherin gene (<jats:italic>CDH1<\/jats:italic>) is associated with hereditary diffuse gastric cancer (HDGC), a rare autosomal dominant syndrome predisposing to both diffuse gastric cancer (DGC) and lobular breast cancer (LBC). We searched for <jats:italic>CDH1<\/jats:italic> germline defects in 32 HDGC Italian probands selected according to international consensus criteria and in 5 selected relatives. We used a series of molecular methods, including: DNA sequencing, multiplex ligation\u2010dependent probe amplification, single\u2010nucleotide primer extension, bisulfite sequencing, reverse\u2010transcription PCR, and bioinformatics tools. We identified pathogenic mutations in 6 out of 32 probands (19%): one truncating and two missense mutations, one large deletion, one allelic expression imbalance and one splicing defect. Three out of six <jats:italic>CDH1<\/jats:italic> constitutive alterations were novel. Our data support the need for a multimethod approach for <jats:italic>CDH1<\/jats:italic> genetic testing, demonstrating that both DNA and RNA analyses are required to increase the detection rate of pathogenic mutations, thus reducing the number of patients without a clear molecular diagnosis. On the whole, our results indicate that not only DGC patients, but also subjects with personal or family history of LBC might benefit from <jats:italic>CDH1<\/jats:italic> genetic testing. Moreover, our findings support the notion that prophylactic gastrectomy should be offered to asymptomatic <jats:italic>CDH1<\/jats:italic> mutation carriers; indeed, while endoscopic analysis with histological examination of random gastric biopsies can miss cancer foci, gastrectomy performed in these subjects always revealed foci of cancer cells. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/gcc.22155","type":"journal-article","created":{"date-parts":[[2014,2,4]],"date-time":"2014-02-04T03:18:58Z","timestamp":1391483938000},"page":"432-445","source":"Crossref","is-referenced-by-count":26,"title":["Complementary molecular approaches reveal heterogeneous CDH1 germline defects in Italian patients with hereditary diffuse gastric cancer (HDGC) syndrome"],"prefix":"10.1002","volume":"53","author":[{"given":"Valeria","family":"Molinaro","sequence":"first","affiliation":[{"name":"Department of Biology and Biotechnology University of Pavia Pavia 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