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 |
|---|---|
| Pages (from-to) | 5401-5409 |
| Number of pages | 9 |
| Journal | Clinical Cancer Research |
| Volume | 11 |
| Issue number | 15 |
| DOIs | |
| State | Published - Aug 1 2005 |
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All Science Journal Classification (ASJC) codes
- Cancer Research
- Oncology
Cite this
Characterization of a recurrent germ line mutation of the E-cadherin gene : Implications for genetic testing and clinical management. / 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 T.; Huntsman, David G.
In: Clinical Cancer Research, Vol. 11, No. 15, 01.08.2005, p. 5401-5409.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characterization of a recurrent germ line mutation of the E-cadherin gene
T2 - Implications for genetic testing and clinical management
AU - Suriano, Gianpaolo
AU - Yew, Sandie
AU - Ferreira, Paulo
AU - Senz, Janine
AU - Kaurah, Pardeep
AU - Ford, James M.
AU - Longacre, Teri A.
AU - Norton, Jeffrey A.
AU - Chun, Nicki
AU - Young, Sean
AU - Oliveira, Maria J.
AU - MacGillivray, Barbara
AU - Rao, Arundhati
AU - Sears, Dawn
AU - Jackson, Charles E.
AU - Boyd, Jeff
AU - Yee, Cindy
AU - Deters, Carolyn
AU - Pai, G. Shashidhar
AU - Hammond, Lyn S.
AU - McGivern, Bobbi J.
AU - Medgyesy, Diane
AU - Sartz, Denise
AU - Arun, Banu
AU - Oelschlager, Brant K.
AU - Upton, Mellisa P.
AU - Neufeld-Kaiser, Whitney
AU - Silva, Orlando E.
AU - Donenberg, Talia R.
AU - Kooby, David A.
AU - Sharma, Shobha
AU - Jonsson, Björn Anders
AU - Gronberg, Henrik
AU - Gallinger, Steve
AU - Seruca, Raquel
AU - Lynch, Henry T.
AU - Huntsman, David G.
PY - 2005/8/1
Y1 - 2005/8/1
N2 - 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
AB - 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
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UR - http://www.scopus.com/inward/citedby.url?scp=23044486914&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-05-0247
DO - 10.1158/1078-0432.CCR-05-0247
M3 - Article
C2 - 16061854
AN - SCOPUS:23044486914
VL - 11
SP - 5401
EP - 5409
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 15
ER -