Abstract
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 mis-sense 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 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
Original language | English (US) |
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Pages (from-to) | 5401-5409 |
Number of pages | 9 |
Journal | Clinical Cancer Research |
Volume | 11 |
Issue number | 15 |
DOIs | |
State | Published - Aug 1 2005 |
All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research