scholarly journals Predicting Pathogenicity of CDH1 Gene Variants in Patients with Early-onset Diffuse Gastric Cancer from Western Mexico

2021 ◽  
Author(s):  
Azaria García-Ruvalcaba ◽  
Lourdes del C. Rizo de la Torre ◽  
María T. Magaña-Torres ◽  
Ernesto Prado-Montes-de-Oca ◽  
Andrea V. Ruiz-Ramírez ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Onset ◽  
Diffuse Gastric Cancer ◽  
Gene Variants ◽  
Cdh1 Gene ◽  
Western Mexico

Detection of CDH1 Gene Variants in Early-onset Diffuse Gastric Cancer in Chinese Patients

2014 ◽  
Vol 60 (11/2014) ◽  
Author(s):  
Xu Yanjun ◽  
Cao Wenming ◽  
Ying Lisha ◽  
Xu Qi ◽  
Guo Jianmin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Onset ◽  
Chinese Patients ◽  
Diffuse Gastric Cancer ◽  
Gene Variants ◽  
Cdh1 Gene

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.

Searching for CDH1 gene mutations in early-onset diffuse gastric cancer in Chinese patients.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 23-23
Author(s):  
Xu Yanjun ◽  
Cao Wenming ◽  
Xu Qi ◽  
Guo Jianmin ◽  
Wang Xinbao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Gene Mutations ◽  
Germline Mutations ◽  
Chinese Patients ◽  
Diffuse Gastric Cancer ◽  
Cdh1 Gene ◽  
Node Metastasis ◽  
Cdh1 Mutation

23 Background: CDH1 germline mutations are found to be associated with the development of hereditary diffuse gastric cancer (HDGC) and the early-onset diffuse gastric cancer (EODGC). But the impact of CDH1 gene mutations and large deletions on HDGC and EODGC has not been fully determined in Asians. Although the incidence of gastric cancer is relatively high in China, the detection rate of CDH1 germline mutations in Chinese patients with EODGC is rare compared to that in European patients. Methods: We investigated the mutation status of the CDH1 gene in 57 Chinese EODGC patients younger than 40 years old who met the clinical criteria for HDGC. Polymerase chain reaction-direct sequencing was performed, and multiplex ligation-dependent probe amplification (MLPA) was used to evaluate the patients with negative sequencing results. Associations between mutation, clinicopathologic, and overall survival data were analyzed by SPSS 19. Results: The germline mutations of CDH1gene were identified in 51 (89.5%) of the 57 EODGC patients. The nonsense mutation in exon 13 (c.2200T>C, p.Ala692*) occurred in fourty-six EODGC patients. The missense mutations were detected in twenty patients (Eighteen in exon 5: c.778G>C, p.Glu218Asp; Two in exon 12: c.2012C>G, p.Leu630Val). No deletion or duplication in any patient. Most of the patients carrying the CDH1 mutation in exon 13 had lymph node metastasis when compared with patients lacking CDH1 mutation (87.2% vs 60.0%) ( P < 0.05 ). EODGC patients, lacking germline CDH1 alterations, showed a longer median overall survival (mOS) than patients carrying CDH1 mutation in exon 13 ( P < 0.05 ). Moreover, the presence of CDH1 mutation in exon 13 was associated with the incidence of neural invasion ( P < 0.05 ). Conclusions: This study reveals novel CDH1 mutations in Chinese EODGC patients which had been poorly investigated. The presence of CDH1 mutation in EODGC patients may result in lymph node metastasis and poor prognosis. More research is needed to determine additional genetic targets that trigger EODGC.

scholarly journals Germline CDH1 mutations are a significant contributor to the high frequency of early-onset diffuse gastric cancer cases in New Zealand Māori

2018 ◽  
Vol 18 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Christopher Hakkaart ◽  
Lis Ellison-Loschmann ◽  
Robert Day ◽  
Andrew Sporle ◽  
Jonathan Koea ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
New Zealand ◽  
High Frequency ◽  
Early Onset ◽  
Diffuse Gastric Cancer ◽  
Significant Contributor

CDH-1 germ line mutations in diffuse gastric and infiltrating ductal breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22218-e22218
Author(s):  
A. P. Efremidis ◽  
F. Fostira ◽  
C. Panopoulos ◽  
K. Papademitriou ◽  
N. Pistalmazian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Positive Family History ◽  
Bilateral Breast Cancer ◽  
Hereditary Diffuse Gastric Cancer ◽  
Bilateral Mastectomy ◽  
Diffuse Gastric Cancer ◽  
Cancer Type ◽  
Diffuse Type ◽  
Cdh1 Gene

e22218 Background: Hereditary Diffuse Gastric Cancer (HDGC) syndrome is characterized by the predisposition to gastric cancer of the diffuse type and to breast cancer of the lobular type. The autosomal dominantly inherited germline mutations of the E- cadherin (CDH1) gene are the defects underlying the HDGC syndrome. The median age of onset for diffuse gastric cancer is 38 years. CDH1 mutations are highly penetrant, conferring a cumulative risk of diffuse gastric cancer of 75%. Methods: Genomic DNA was purified from peripheral blood leukocytes following standard chloroform extraction. The complete coding sequences of the CDH1-gene, including splice junctions, were amplified by Polymerase Chain Reaction (PCR) and electrophorized in an ABI Prism 310 Genetic Analyzer. Results: A pathogenic mutation located on exon 7 of the CDH1 gene was identified in a female patient diagnosed with bilateral breast cancer at the age of 36. She underwent bilateral mastectomy for an infiltrating ductal adenocarcinoma of the left breast and in situ lobular of the right breast. At the age of 45 the patient underwent gastrectomy for diffuse type gastric adenocarcinoma. She had a positive family history for breast and gastric cancer from both sides, but without meeting the absolute clinical criteria for hereditary diffuse gastric cancer syndrome. The nonsense mutation found was probably maternally inherited, since the maternal grandmother was diagnosed with breast cancer at the age of 38. Conclusions: The selection process of patients for genetic testing for the HDGC syndrome is not quite clear at the moment, as it is apparent that more types of breast cancer and not only lobular, can be associated with the syndrome. Criteria should be more flexible in respects to the histopathology of the cancer type. This is the first CDH1 mutation identified in a Greek patient. No significant financial relationships to disclose.

A Case of Familial Diffuse Gastric Cancer as a Result of a Novel CDH1 Gene Mutation

2012 ◽  
Vol 107 ◽  
pp. S296
Author(s):  
Rebecca Rawl ◽  
Heather Brooks ◽  
Martin Scobey ◽  
Amit Aravapalli
Keyword(s):  
Gastric Cancer ◽  
Gene Mutation ◽  
Diffuse Gastric Cancer ◽  
Cdh1 Gene

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
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