Characterization of a recurrent germ line mutation of the E-cadherin gene: Implications for genetic testing and clinical management Journal Article
| Authors: | Suriano, G.; Yew, S.; Ferreira, P.; Senz, J.; Kaurah, P.; Ford, J. M.; Longacre, T. A.; Norton, J. A.; Chun, N.; Young, S.; Oliveira, M. J.; MacGillivray, B.; Rao, A.; Sears, D.; Jackson, C. E.; Boyd, J.; Yee, C.; Deters, C.; Pai, G. S.; Hammond, L. S.; McGivern, B. J.; Medgyesy, D.; Sartz, D.; Arun, B.; Oelschlager, B. K.; Upton, M. P.; Neufeld-Kaiser, W.; Silva, O. E.; Donenberg, T. R.; Kooby, D. A.; Sharma, S.; Jonsson, B. A.; Grönberg, H.; Gallinger, S.; Seruca, R.; Lynch, H.; Huntsman, D. G. |
| Article Title: | Characterization of a recurrent germ line mutation of the E-cadherin gene: Implications for genetic testing and clinical management |
| 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 <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. © 2005 American Association for Cancer Research. |
| Keywords: | adult; aged; aged, 80 and over; middle aged; gene mutation; missense mutation; codon, nonsense; exons; mutation, missense; genetic analysis; polymerase chain reaction; protein function; cancer prevention; haplotypes; cancer screening; practice guideline; heterozygote; uvomorulin; risk; pedigree; germ line; blotting, western; collagen; gastrectomy; stomach cancer; plasmids; dna sequence; familial cancer; neoplasm invasiveness; high performance liquid chromatography; chromatography, high pressure liquid; high risk population; dna mutational analysis; dna primers; drug combinations; genetic screening; cadherins; stomach neoplasms; germ-line mutation; laminin; sequence analysis, dna; proteoglycans |
| Journal Title: | Clinical Cancer Research |
| Volume: | 11 |
| Issue: | 15 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2005-08-01 |
| Start Page: | 5401 |
| End Page: | 5409 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-05-0247 |
| PUBMED: | 16061854 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 69" - "Export Date: 24 October 2012" - "CODEN: CCREF" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work