Tu1377 No CDH1 Germline Mutations Identified in a Large Cohort of Very Early-Onset Diffuse Gastric Cancer

2016 ◽  
Vol 150 (4) ◽  
pp. S889
Author(s):  
Melyssa Aronson ◽  
Carol Swallow ◽  
Christine Brezden-Masley ◽  
Kara Semotiuk ◽  
Savtaj Brar ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Onset ◽  
Germline Mutations ◽  
Large Cohort ◽  
Diffuse Gastric Cancer

Prevalence of CDH1 germline mutations in subjects with early onset or familial lobular breast cancer, a multicenter collaboration

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11042-11042
Author(s):  
S. Masciari ◽  
K. A. Schrader ◽  
J. Senz ◽  
N. Tung ◽  
J. Balmana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Family History ◽  
Early Onset ◽  
Direct Sequencing ◽  
Familial Cancer ◽  
Germline Mutations ◽  
Diffuse Gastric Cancer ◽  
Prophylactic Gastrectomy ◽  
History Of

11042 Background: Invasive lobular breast carcinoma (LBC) is part of the hereditary diffuse gastric cancer (HDGC) syndrome, associated with germline mutations in the E-cadherin (CDH1) gene. CDH1 mutations can be identified in 80% of families ascertained by DGC. The risk of DGC in CDH1 mutation carriers is 67% in males, and 83% in females; the estimated risk of LBC in women is 39–50% to age 80. Management of HDGC includes prophylactic gastrectomy. In this study, we estimated the prevalence of germline CDH1mutations among women with LBC who were either diagnosed at young age or had family history of breast cancer (BC). Methods: Germline DNA was collected from 383 women with LBC or mixed, lobular/ductal, BC from breast cancer programs, familial cancer clinics, and population-based cohorts. Germline BRCA1or BRCA2mutations carriers were excluded. Eligible women had (1) LBC before age 45 or (2) LBC at any age with at least two 1st or 2nd degree relatives with BC of any type. Denaturing high pressure liquid chromatography was undertaken, followed by direct sequencing of exons displaying changes. Results: At the time of submission 310 of 383 samples have been fully sequenced. One previously characterized missense mutation and four novel non-synonymous variants (1.6%) were found. Three of these women had LBC before 45 years and no family history of BC; two had BC family history. No gastric cancers were reported in these families. Functional assays to assess the pathogenicity of the variants are in process. Conclusions: These results confirm that CDH1 is responsible for a small proportion of familial and early onset LBC. Given the difficulty of identifying CDH1 mutations from BC history alone and the importance of managing the gastric cancer risk in CDH1carriers, these findings should underscore the need to obtain an accurate abdominal cancer family history from women with LBC. No significant financial relationships to disclose.

1066 - Phenotypic Expression of Cdh1 Germline Mutations Unselected for Hereditary Diffuse Gastric Cancer

2018 ◽  
Vol 154 (6) ◽  
pp. S-204
Author(s):  
Nicolette J. Rodriguez ◽  
Patrick Reineke ◽  
Holly LaDuca ◽  
Rosa M. Xicola ◽  
Xavier Llor
Keyword(s):  
Gastric Cancer ◽  
Phenotypic Expression ◽  
Germline Mutations ◽  
Hereditary Diffuse Gastric Cancer ◽  
Diffuse Gastric Cancer

CDH1 germline mutations in healthy individuals from families with the hereditary diffuse gastric cancer syndrome

2021 ◽  
pp. jmedgenet-2021-108226
Author(s):  
Giovanni Corso ◽  
Francesca Magnoni ◽  
Giulia Massari ◽  
Cristina Maria Trovato ◽  
Alessandra Margherita De Scalzi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Healthy Subjects ◽  
Relevant Literature ◽  
Germline Mutations ◽  
Hereditary Diffuse Gastric Cancer ◽  
Diffuse Gastric Cancer ◽  
Missense Mutations ◽  
Healthy Individuals ◽  
Cancer Syndrome ◽  
The Difference

The objective of this study was to determining the frequency of different sub-types of pathogenic CDH1 germline mutations in healthy and asymptomatic individuals from families with the hereditary diffuse gastric cancer (HDGC) syndrome. Relevant literature dating from 1998 to 2019 was systematically searched for data on CDH1 germline mutations. The collected variants were classified according to their subtype into the following classes: missense, non-sense, splicing, insertions and deletions. The χ2 test was used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was statistically significant. CDH1 genetic screening data were retrieved for 224 patients with GC and 289 healthy individuals. Among the subjects that had tested CDH1 positive, splicing mutations were found in 30.4% of the healthy individuals and in 15.2% of the patients with GC (p=0.0076). Missense mutations were also found to occur in healthy subjects with higher frequency (22.2%) than in GC-affected individuals (18.3%), but the difference was not significant in this case. In families meeting the clinical criteria for the HDGC syndrome, CDH1 splicing and missense germline mutations have been reported to occur with higher frequency in healthy subjects than in patients with cancer. This preliminary observation suggests that not all pathogenic CDH1 germline mutations confer the same risk of developing GC.

scholarly journals Germline mutations of the E-cadherin gene in families with inherited invasive lobular breast carcinoma but no diffuse gastric cancer

Cancer ◽  
2011 ◽  
Vol 117 (14) ◽  
pp. 3112-3117 ◽  
Author(s):  
Ze Ming Xie ◽  
Lai Sheng Li ◽  
Claire Laquet ◽  
Frédérique Penault-Llorca ◽  
Nancy Uhrhammer ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Breast Carcinoma ◽  
Germline Mutations ◽  
Diffuse Gastric Cancer ◽  
Lobular Breast Carcinoma ◽  
E Cadherin

scholarly journals CDH1/E-cadherin germline mutations in early-onset gastric cancer

2006 ◽  
Vol 43 (11) ◽  
pp. 867-872 ◽  
Author(s):  
J T Bacani ◽  
M Soares ◽  
R Zwingerman ◽  
N di Nicola ◽  
J Senz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Onset ◽  
Germline Mutations ◽  
E Cadherin

scholarly journals Early-onset diffuse gastric cancer associated with a de novo large genomic deletion of CDH1 gene

2013 ◽  
Vol 17 (4) ◽  
pp. 745-749 ◽  
Author(s):  
Shinya Sugimoto ◽  
Hidetaka Yamada ◽  
Masazumi Takahashi ◽  
Yuichi Morohoshi ◽  
Naotaka Yamaguchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Onset ◽  
De Novo ◽  
Diffuse Gastric Cancer ◽  
Cdh1 Gene ◽  
Genomic Deletion ◽  
Large Genomic Deletion

Variable penetrance of CDH1 mutation diffuse gastric cancer: A genomic analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4082-4082
Author(s):  
David Paul Kelsen ◽  
Kasmintan A. Schrader ◽  
Raya Khanin ◽  
Laura H. Tang ◽  
Erin E. Salo-Mullen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Early Onset ◽  
Germ Line ◽  
Diffuse Gastric Cancer ◽  
Second Hit ◽  
Whole Exome ◽  
Prophylactic Gastrectomy ◽  
Variable Penetrance

4082 Background: CDH1 encodes E-cadherin; mutations (CDH1mut) increase the risk of diffuse gastric (DGC) and lobular breast cancers. Life-time risk of DGC is estimated at 80%. Current recommendations are prophylactic gastrectomy (PG) in CDH1mut carriers after age 20. Foci of DGC are found in some PG; others have none at PG, and some CDH1mut without PG never develop cancer. Identifying risk modifying alleles or other genomic events which increase the risk of DGC may improve understanding of DGC and may provide a biomarker for when to perform PG. Methods: For a Gastric Cancer Registry, we collected family pedigrees, germline DNA and FFPE tumor from CDH1mut DGC patients (pts) and their families. From 24 families, with 52 CDH1mut individuals, we identified 4 families in which a young CDH1mut pt developed advanced DGC while their CDH1mut parent and siblings had no clinical evidence of DGC. Several relatives had undergone PG with no DGC found. We hypothesize that there are risk modifying alleles and/or a “second hit” that causes variable penetrance and early onset of DGC in the young CDH1mut pts. Whole genome sequencing was performed on germ line DNA (Complete Genomics, Inc. Mountain View, CA); and whole exome sequencing on tumor specimens (MSKCC). Results: To date, 4 DGC pts and 8 relatives from 4 families have been studied. All 4 affected pts were women (ages 17, 25, 27, 42); their unaffected CDH1mut parents were 41, 51, 54, and 70 years old. The families are of Kenyan, Scandinavian, Italian, Eastern European, and Scottish origin. CDH1 mutations for the pts and their families were confirmed on WGS, and were as follows: 1451C>A(pro484his);c. 1792C>T (arg598ter);c. 1893dupA in exon 12;c. 1565+1G>A (IVS10+1G>A). Analysis of germline DNA for modifying alleles is being performed (Ingenuity Systems, Redwood, Ca.); whole exome sequencing of tumor to identify a possible "second hit" is underway. These data will be presented. Conclusions: Since at least some older pts with proven CDH-1mut do not develop DGC while their children do, CGH-1mut alone may not be sufficient to cause early onset DGC. We hope to identify the additional genomic events associated with early onset advanced DGC. Supported in part by grants from the Gerstner and DeGregorio Foundations.

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