Characterization of a recurrent germ line mutation of the E-cadherin gene: implications for genetic testing and clinical management.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Suriano Gianpaolo, Yew Sandie, Ferreira Paulo, Senz Janine, Kaurah Pardeep, Ford James M, Longacre Teri A, Norton Jeffrey A, Chun Nicki, Young Sean, Oliveira Maria J, Macgillivray Barbara, Rao Arundhati, Sears Dawn, Jackson Charles E, Boyd Jeff, Yee Cindy, Deters Carolyn, Pai G Shashidhar, Hammond Lyn S, McGivern Bobbi J, Medgyesy Diane, Sartz Denise, Arun Banu, Oelschlager Brant K, Upton Mellisa P, Neufeld-Kaiser Whitney, Silva Orlando E, Donenberg Talia R, Kooby David A, Sharma Shobha, Jonsson Björn-Anders, Gronberg Henrik, Gallinger Steve, Seruca Raquel, Lynch Henry, Huntsman David G
Аннотация
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.
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>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 <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>T mutation carriers.
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 <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.