Characterization of a recurrent germ line mutation of the E-cadherin gene: Implications for genetic testing and clinical management

• Type: Article in International Scientific Journal
• Date: 2005

Authors

Jonsson, BA (Author) Other; Gronberg, H (Author) Other; Gallinger, S (Author) Other; Seruca, R (Author) FMUP; Lynch, H (Author) Other; Huntsman, DG (Author) Other; Suriano, G (Author) Other; Yew, S (Author) Other; Ferreira, P (Author) Other; Senz, J (Author) Other; Kaurah, P (Author) Other; Ford, JM (Author) Other; Longacre, TA (Author) Other; Norton, JA (Author) Other; Chun, N (Author) Other; Young, S (Author) Other; Oliveira, MJ (Author) Other; MacGillivray, B (Author) Other; Rao, A (Author) Other; Sears, D (Author) Other; Jackson, CE (Author) Other; Boyd, J (Author) Other; Yee, C (Author) Other; Deters, C (Author) Other; Pai, GS (Author) Other; Hammond, LS (Author) Other; McGivern, BJ (Author) Other; Medgyesy, D (Author) Other; Sartz, D (Author) Other; Arun, B (Author) Other; Oelschlager, BK (Author) Other; Upton, MP (Author) Other; Neufeld Kaiser, W (Author) Other; Silva, OE (Author) Other; Donenberg, TR (Author) Other; Kooby, DA (Author) Other; Sharma, S (Author) Other

Journal

Title: Clinical Cancer Research

Vol. 11

Pages: 5401-5409

ISSN: 1078-0432

Publisher: American Association for Cancer Research

Indexing

ISI Web of Knowledge - 118 Citations

Scopus - 112 Citations

Other information

Authenticus ID: P-000-20R

DOI: 10.1158/1078-0432.ccr-05-0247

Abstract (EN): Purpose: To identify germ line CDH1 mutations in hereditary diffuse gastric cancer (HDGC) families and develop guidelines for management of at risk individuals. 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9