Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer

• Published in: JAMA
• Main Authors: Pardeep Kaurah, Andree Macmillan, Niki Boyd, Janine Senz, Alessandro De Luca, Nicki Chun, Gianpaolo Suriano, Sonya Zaor, Lori Van Manen, Cathy Gilpin, Sarah Nikkel, Mary Connolly Wilson, Scott Weissman, Wendy S. Rubinstein, Courtney Sebold, Robert Greenstein, Jennifer Stroop, Dwight Yim, Benoit Panzini, Wendy Mckinnon, Marc Greenblatt, Debrah Wirtzfeld, Daniel Fontaine, Daniel Coit, Sam Yoon, Daniel Chung, Gregory Lauwers, Carlos Vaccaro, Maria Ana Redal, Carla Oliveira, Marc Tischkowitz, Sylviane Olschwang, Steven Gallinger, Henry Lynch, Jane Green, James Ford, Paul Pharoah, Bridget Fernandez, David Huntsman, PIZZUTI, Antonio
• Other Authors: Pardeep, Kaurah, Andree, Macmillan, Niki, Boyd, Janine, Senz, Alessandro De, Luca, Nicki, Chun, Gianpaolo, Suriano, Sonya, Zaor, Lori Van, Manen, Cathy, Gilpin, Sarah, Nikkel, Mary Connolly, Wilson, Scott, Weissman, Wendy S., Rubinstein, Courtney, Sebold, Robert, Greenstein, Jennifer, Stroop, Dwight, Yim, Benoit, Panzini, Wendy, Mckinnon, Marc, Greenblatt, Debrah, Wirtzfeld, Daniel, Fontaine, Daniel, Coit, Sam, Yoon, Daniel, Chung, Gregory, Lauwer, Pizzuti, Antonio, Carlos, Vaccaro, Maria Ana, Redal, Carla, Oliveira, Marc, Tischkowitz, Sylviane, Olschwang, Steven, Gallinger, Henry, Lynch, Jane, Green, James, Ford, Paul, Pharoah, Bridget, Fernandez, David, Huntsman
• Format: Article in Journal/Newspaper
• Language: English
• Published: AMER MEDICAL ASSOC 2007
• Subjects: Newfoundland
• Online Access: http://hdl.handle.net/11573/366499; https://doi.org/10.1001/jama.297.21.2360; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000247007200018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=0c7ff228ccbaaa74236f48834a34396a; http://www.scopus.com/inward/record.url?eid=2-s2.0-34249989159&partnerID=65&md5=10e5039f9bba75c0b88aea468686d4c1

Context Hereditary diffuse gastric cancer is caused by germline mutations in the epithelial cadherin ( CDH1) gene and is characterized by an increased risk for diffuse gastric cancer and lobular breast cancer. Objective To determine whether recurring germline CDH1 mutations occurred due to independent mutational events or common ancestry. Design, Setting, and Patients Thirty-eight families diagnosed clinically with hereditary diffuse gastric cancer were accrued between November 2004 and January 2006 and were analyzed for CDH1 mutations as part of an ongoing study at the British Columbia Cancer Agency. Twenty-six families had at least 2 gastric cancer cases with 1 case of diffuse gastric cancer in a person younger than 50 years; 12 families had either a single case of diffuse gastric cancer diagnosed in a person younger than 35 years or multiple cases of diffuse gastric cancer diagnosed in persons older than 50 years. Main Outcome Measures Classification of family members as carriers or noncarriers of CDH1 mutations. Haplotype analysis to assess recurring mutations for common ancestry was performed on 7 families from this study and 7 previously reported families with the same mutations. Results Thirteen mutations ( 6 novel) were identified in 15 of the 38 families ( 40% detection rate). The 1137G > A splicing mutation and the 1901C > T ( A634V) missense/splicing mutation occurred on common haplotypes in 2 families but on different haplotypes in a third family. The 2195G > A ( R732Q) missense/splicing mutation occurred in 2 families on different haplotypes. The 2064-2065delTG mutation occurred on a common haplotype in 2 families. Two families from this study plus 2 additional families carrying the novel 2398delC mutation shared a common haplotype, suggesting a founder effect. All 4 families originate from the southeast coast of Newfoundland. Due to concentrations of lobular breast cancer cases, 2 branches of this family had been diagnosed as having hereditary breast cancer and were tested for BRCA ...