{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T07:48:15Z","timestamp":1769845695235,"version":"3.49.0"},"reference-count":33,"publisher":"American Association for Cancer Research (AACR)","issue":"15","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Purpose: To identify germ line CDH1 mutations in hereditary diffuse gastric cancer (HDGC) families and develop guidelines for management of at risk individuals.<\/jats:p>\n               <jats:p>Experimental Design: We ascertained 31 HDGC previously unreported families, including 10 isolated early-onset diffuse gastric cancer (DGC) cases. Screening for CDH1 germ line mutations was done by denaturing high-performance liquid chromatography and automated DNA sequencing.<\/jats:p>\n               <jats:p>Results: We identified eight inactivating and one missense CDH1 germ line mutation. The missense mutation conferred in vitro loss of protein function. Two families had the previously described 1003C&amp;gt;T nonsense mutation. Haplotype analysis revealed this to be a recurrent and not a founder mutation. Thirty-six percent (5 of 14) of the families with a documented DGC diagnosed before the age of 50 and other cases of gastric cancer carried CDH1 germ line mutations. Two of 10 isolated cases of DGC in individuals ages &amp;lt;35 years harbored CDH1 germ line mutations. One mutation positive family was ascertained through a family history of lobular breast cancer (LBC) and another through an individual with both DGC and LBC. Occult DGC was identified in five of six prophylactic gastrectomies done on asymptomatic, endoscopically negative 1003C&amp;gt;T mutation carriers.<\/jats:p>\n               <jats:p>Conclusions: In addition to families with a strong history of early-onset DGC, CDH1 mutation screening should be offered to isolated cases of DGC in individuals ages &amp;lt;35 years and for families with multiple cases of LBC, with any history of DGC or unspecified GI malignancies. Prophylactic gastrectomy is potentially a lifesaving procedure and clinical breast screening is recommended for asymptomatic mutation carriers.<\/jats:p>","DOI":"10.1158\/1078-0432.ccr-05-0247","type":"journal-article","created":{"date-parts":[[2005,9,21]],"date-time":"2005-09-21T23:49:34Z","timestamp":1127346574000},"page":"5401-5409","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["Characterization of a Recurrent Germ Line Mutation of the <i>E-Cadherin<\/i> Gene: Implications for Genetic Testing and Clinical Management"],"prefix":"10.1158","volume":"11","author":[{"given":"Gianpaolo","family":"Suriano","sequence":"first","affiliation":[{"name":"1Pathology and Laboratory Medicine and Departments of"},{"name":"5Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal;"}]},{"given":"Sandie","family":"Yew","sequence":"additional","affiliation":[{"name":"3Hereditary Cancer Program, British Columbia Cancer Agency; and"}]},{"given":"Paulo","family":"Ferreira","sequence":"additional","affiliation":[{"name":"5Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal;"}]},{"given":"Janine","family":"Senz","sequence":"additional","affiliation":[{"name":"4Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada;"}]},{"given":"Pardeep","family":"Kaurah","sequence":"additional","affiliation":[{"name":"3Hereditary Cancer Program, British Columbia Cancer Agency; and"}]},{"given":"James M.","family":"Ford","sequence":"additional","affiliation":[{"name":"6Division of Oncology, Departments of Medicine and Genetics,"}]},{"given":"Teri A.","family":"Longacre","sequence":"additional","affiliation":[{"name":"7Pathology, and"}]},{"given":"Jeffrey A.","family":"Norton","sequence":"additional","affiliation":[{"name":"8Surgery, Stanford University School of Medicine, Stanford, California;"}]},{"given":"Nicki","family":"Chun","sequence":"additional","affiliation":[{"name":"6Division of Oncology, Departments of Medicine and Genetics,"}]},{"given":"Sean","family":"Young","sequence":"additional","affiliation":[{"name":"1Pathology and Laboratory Medicine and Departments of"}]},{"given":"Maria J.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"5Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal;"}]},{"given":"Barbara","family":"MacGillivray","sequence":"additional","affiliation":[{"name":"2Medical Genetics, University of British Columbia;"},{"name":"3Hereditary Cancer Program, British Columbia Cancer Agency; and"}]},{"given":"Arundhati","family":"Rao","sequence":"additional","affiliation":[{"name":"9Scott and White Clinic, Temple, Texas;"}]},{"given":"Dawn","family":"Sears","sequence":"additional","affiliation":[{"name":"9Scott and White Clinic, Temple, Texas;"}]},{"given":"Charles E.","family":"Jackson","sequence":"additional","affiliation":[{"name":"10Departments of Surgery and Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York;"}]},{"given":"Jeff","family":"Boyd","sequence":"additional","affiliation":[{"name":"10Departments of Surgery and Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York;"}]},{"given":"Cindy","family":"Yee","sequence":"additional","affiliation":[{"name":"10Departments of Surgery and Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York;"}]},{"given":"Carolyn","family":"Deters","sequence":"additional","affiliation":[{"name":"11Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebraska;"}]},{"given":"G. Shashidhar","family":"Pai","sequence":"additional","affiliation":[{"name":"12Division of Genetics, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina;"}]},{"given":"Lyn S.","family":"Hammond","sequence":"additional","affiliation":[{"name":"12Division of Genetics, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina;"}]},{"given":"Bobbi J.","family":"McGivern","sequence":"additional","affiliation":[{"name":"13Department of Clinical Cancer Genetics,"}]},{"given":"Diane","family":"Medgyesy","sequence":"additional","affiliation":[{"name":"15Front Range Cancer Specialists, Ft. Collins, Colorado; Deparments of"}]},{"given":"Denise","family":"Sartz","sequence":"additional","affiliation":[{"name":"15Front Range Cancer Specialists, Ft. Collins, Colorado; Deparments of"}]},{"given":"Banu","family":"Arun","sequence":"additional","affiliation":[{"name":"14Breast Medical Oncology, M.D. Anderson Cancer Centre, Houston, Texas;"}]},{"given":"Brant K.","family":"Oelschlager","sequence":"additional","affiliation":[{"name":"16Surgery,"}]},{"given":"Mellisa P.","family":"Upton","sequence":"additional","affiliation":[{"name":"11Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebraska;"},{"name":"17Pathology, and"}]},{"given":"Whitney","family":"Neufeld-Kaiser","sequence":"additional","affiliation":[{"name":"18Genetics, University of Washington, Seattle, Washington;"}]},{"given":"Orlando E.","family":"Silva","sequence":"additional","affiliation":[{"name":"19Jackson Health System University of Miami School of Medicine, Miami, Florida;"}]},{"given":"Talia R.","family":"Donenberg","sequence":"additional","affiliation":[{"name":"19Jackson Health System University of Miami School of Medicine, Miami, Florida;"}]},{"given":"David A.","family":"Kooby","sequence":"additional","affiliation":[{"name":"20Division of Surgical Oncology and"}]},{"given":"Shobha","family":"Sharma","sequence":"additional","affiliation":[{"name":"21Department of Pathology, Emory University Medical Center, Atlanta, Georgia;"}]},{"given":"Bjo\u0308rn-Anders","family":"Jonsson","sequence":"additional","affiliation":[{"name":"22Department of Radiation Sciences\/Oncology, Umea University, Umea, Sweden; and"}]},{"given":"Henrik","family":"Gronberg","sequence":"additional","affiliation":[{"name":"22Department of Radiation Sciences\/Oncology, Umea University, Umea, Sweden; and"}]},{"given":"Steve","family":"Gallinger","sequence":"additional","affiliation":[{"name":"23Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital, Toronto, Ontario, Canada"}]},{"given":"Raquel","family":"Seruca","sequence":"additional","affiliation":[{"name":"5Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal;"}]},{"given":"Henry","family":"Lynch","sequence":"additional","affiliation":[{"name":"11Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebraska;"}]},{"given":"David G.","family":"Huntsman","sequence":"additional","affiliation":[{"name":"1Pathology and Laboratory Medicine and Departments of"},{"name":"3Hereditary Cancer Program, British Columbia Cancer Agency; and"},{"name":"4Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada;"}]}],"member":"1086","published-online":{"date-parts":[[2005,8,1]]},"reference":[{"key":"2022061104140255000_B1","doi-asserted-by":"crossref","unstructured":"La Vecchia C, Lucchini F, Negri E, Boyle P, Maisonneuve P, Levi F. 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